Role of Linoleic Acid Hydroperoxide Preformed by Cyclooxygenase-1 or -2 on the Regulation of Prostaglandin Formation from Arachidonic Acid by the Respective Enzyme

Linoleic acid (LA) preincubated with cyclooxygenase (COX)-1 or -2 inhibited prostaglandin (PG) formation from arachidonic acid (AA) catalyzed by the respective enzyme, but LA without the preincubation did not. 13S-Hydroperoxy-9Z,11E-octadecadienoic acid (13-HPODE) a hydroperoxy adduct of LA inhibited PG formation catalyzed by COX-1 or -2. 13S-Hydroxy-9Z,11E-octadecadienoic acid had no effect on both COX-1 and -2 activities. These results suggest that 13-HPODE which is preformed from LA by COX reaction under normal physiological conditions can be a basal suppressor of PG formation from AA

Effects of Lipid Peroxidation-Derived Products on the Growth of Human Colorectal Cancer Cell Line HT-29

Epidemiologic investigations indicate a close relationship between colorectal cancer and fat intake. However, to date the effects of lipid peroxidation-derived products that are formed from fat (especially free or esterified unsaturated fatty acids) on the initiation or progression of colorectal cancer have not been investigated extensively. Therefore, in the present study, we examined the effects of fatty acids, fatty acid hydroperoxides and aldehydes on the growth of human colorectal cancer cell line HT-29. At concentrations of 1 and 10 µM, linoleic, arachidonic and eicosapentaenoic acids, and 13-hydroperoxyoctadecadienoic and 15-hydroperoxyeicosapentaenoic acids had no significant effects on the growth of HT-29 cells. 4-Hydroxynonenal and 4-hydroxyhexenal had no significant effects on the growth of HT-29 cells up to 10 µM, whereas 4-oxononenal potently inhibited HT-29 cell growth (1–10 µM, 16–85% inhibition). Further experiments concerning DNA fragmentation, expression levels of Bax and Bcl-2 mRNA, expression levels of pro-caspase-3 and caspase-3 proteins, and activity of caspase-3 suggested that 4-oxononenal may increase the sensitivity of HT-29 cells to apoptosis through a decreased expression level of Bcl-2 and then increased formation of caspase-3 from pro-caspase-3

cis9, trans11-Conjugated Linoleic Acid Differentiates Mouse 3T3-L1 Preadipocytes into Mature Small Adipocytes through Induction of Peroxisome Proliferator-activated Receptor γ

Dietary conjugated linoleic acid (CLA) has been reported to exhibit a number of therapeutic effects in animal models and patients, such as anti-hypertensive, anti-hyperlipidemic, anti-arteriosclerotic, anti-carcinogenic, and anti-diabetic effects. However, the underlying mechanism is not well-characterized. In the present study, the effects of cis(c)9, trans(t)11-CLA on the differentiation of mouse 3T3-L1 preadipocytes into mature adipocytes were examined. Treatment with c9, t11-CLA in the presence of insulin, dexamethasone, and 3-isobutyl-1-methyl-xanthine (differentiation cocktail) significantly stimulated the accumulation of triacylglycerol. The microscopic observation of cells stained by Oil Red O demonstrated that c9, t11-CLA increases the amount and proportion of small mature adipocytes secreting adiponectin, a benign adipocytokine, when compared to the differentiation cocktail alone. Furthermore, c9, t11-CLA increased bioactive peroxisome proliferator-activated receptor γ (PPARγ) levels in a nuclear extract of 3T3-L1 cells, suggesting the enhancing effect of this fatty acid on the nuclear transmission of PPARγ, a master regulator of adipocyte differentiation, in 3T3-L1 cells. These results suggest that the therapeutic effects of c9, t11-CLA on lifestyle-related diseases are partially due to the enhanced formation of small adipocytes from preadipocytes via PPARγ stimulation

Suzaku Observations of the North Polar Spur: Evidence for Nitrogen Enhancement

We present observations of the North Polar Spur (NPS) using the X-ray Imaging Spectrometer (XIS) aboard the Suzaku X-ray satellite. The NPS is a large region of enhanced soft X-ray and radio emission projected above the plane of the Galaxy, likely produced by a series of supernovae and stellar winds from the nearby Sco-Cen OB association. The exceptional sensitivity and spectral resolution of the XIS below 1 keV allow unprecedented probing of low-energy spectral lines, including CVI (0.37 keV) and NVII (0.50 keV), and we have detected highly-ionized nitrogen toward the NPS for the first time. For this single pointing toward the brightest 3/4 keV emission (l = 26.8 deg, b = +22.0 deg), the best-fit NPS emission model implies a hot (kT ~ 0.3 keV), collisional ionization equilibrium (CIE) plasma with depleted C, O, Ne, Mg, and Fe abundances of less than 0.5 solar, but an enhanced N abundance, with N/O = 4.0 +0.4,-0.5 times solar. The temperature and total thermal energy of the gas suggest heating by one or more supernovae, while the enhanced nitrogen abundance is best explained by enrichment from stellar material that has been processed by the CNO cycle. Due to the time required to develop AGB stars, we conclude that this N/O enhancement cannot be caused by the Sco-Cen OB association, but may result from a previous enrichment episode in the solar neighborhood.Comment: 13 pages, 10 figures, accepted for publication in PASJ (2nd Suzaku Special Issue

Suzaku Observations of the Local and Distant Hot ISM

Suzaku observed the molecular cloud MBM12 and a blank field less than 3 degrees away to separate the local and distant components of the diffuse soft X-ray background. Towards MBM12, a local (D< 275 pc) O VII emission line was clearly detected with an intensity of 3.5 ph cm^{-2} s^{-1} sr^{-1}$ (or line units, LU), and the O VIII flux was <0.34 LU. The origin of this O VII emission could be hot gas in the Local Hot Bubble (LHB), charge exchange between oxygen ions in the solar wind (SWCX) and geocoronal or interplanetary material, or a combination of the two. If entirely from the LHB, the implied temperature and emission measure would predict 1/4 keV emission in excess of observations. There is no evidence in the X-ray light curve or solar wind data for a significant contribution from geocoronal SWCX. In any case, the observed O VII flux represents an upper limit to both the LHB emission and interplanetary SWCX in this direction. The off-cloud observation was performed immediately following the on-cloud. The net off-cloud O VII and O VIII intensities were (respectively) 2.34\pm0.33 and 0.77\pm0.16 LU, after subtracting the on-cloud foreground emission. Assuming the LHB and SWCX components did not change, these increases can be attributed to more distant Galactic disk, halo, or extragalactic emission. If the distant O VII and O VIII emission is from a thermal plasma in collisional equilibrium beyond the Galactic disk, a temperature of (2.1\pm0.1)\times10^6 K with an emission measure of (4\pm0.6)\times10^-3} cm^{-6}pc is inferred.Comment: 10 pages, 8 figures, accepted by PAS

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

The Quiescent Intracluster Medium in the Core of the Perseus Cluster

Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

EWS/ETS Regulates the Expression of the Dickkopf Family in Ewing Family Tumor Cells

BACKGROUND: The Dickkopf (DKK) family comprises a set of proteins that function as regulators of Wnt/beta-catenin signaling and has a crucial role in development. Recent studies have revealed the involvement of this family in tumorigenesis, however their role in tumorigenesis is still remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: We found increased expression of DKK2 but decreased expression of DKK1 in Ewing family tumor (EFT) cells. We showed that EFT-specific EWS/ETS fusion proteins enhance the DKK2 promoter activity, but not DKK1 promoter activity, via ets binding sites (EBSs) in the 5' upstream region. EWS/ETS-mediated transactivation of the promoter was suppressed by the deletion and mutation of EBSs located upstream of the DKK2 gene. Interestingly, the inducible expression of EWS/ETS resulted in the strong induction of DKK2 expression and inhibition of DKK1 expression in human primary mesenchymal progenitor cells that are thought to be a candidate of cell origin of EFT. In addition, using an EFT cell line SK-ES1 cells, we also demonstrated that the expression of DKK1 and DKK2 is mutually exclusive, and the ectopic expression of DKK1, but not DKK2, resulted in the suppression of tumor growth in immuno-deficient mice. CONCLUSIONS/SIGNIFICANCE: Our results suggested that DKK2 could not functionally substitute for DKK1 tumor-suppressive effect in EFT. Given the mutually exclusive expression of DKK1 and DKK2, EWS/ETS regulates the transcription of the DKK family, and the EWS/ETS-mediated DKK2 up-regulation could affect the tumorigenicity of EFT in an indirect manner

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month