Study of the Intracluster and Intergalactic Medium in the Sculptor Supercluster with Suzaku

We studied the high temperature plasma in the direction of the Sculptor supercluster at z=0.108 with Suzaku. Suzaku carried out four observations in the supercluster: namely, A2811, A2811 offset, A2804, A2801 regions in 2005 Nov.--Dec., including the regions beyond the virial radii of these clusters. The study needed precise background estimation because the measured intensity of the redshifted lines, especially those from oxygen, were strongly affected by the the Galactic emission. The spectra taken in the regions outside of the virial radii of the member clusters were used as the background which included both the Galactic and Cosmic X-ray Background (CXB) components. We also used the background data which were taken near the Sculptor supercluster. Temperature and metal abundance profiles were determined to the virial radii of the member clusters, and then we searched for the oxygen line emission in the region outside of the virial radii of the clusters. As a result, the temperature of the clusters decreased toward the virial radii, and the spectral fits for the filament region did not require extra component other than the Galactic and CXB components. We constrained the intensities of O VII and O VIII lines to be less than 8.1 and 5.1 photons cm^-2 s^-1 arcmin^-2, respectively, as 2-sigma upper limits. The intensity of O VII indicates n_H < 1.6e-5 cm^-3 (Z/0.1 Z_solar)^-1/2 (L/25 Mpc)^-1/2, which corresponds to an over density, delta < 60 (Z/0.1 Z_solar)^-1/2 (L/25 Mpc)^-1/2.Comment: 11 pages, 8 figures, accepted for publication in PAS

Search for X-Ray Emission Associated with the Shapley Supercluster with Suzaku

Suzaku performed observations of 3 regions in and around the Shapley supercluster: a region located between A3558 and A3556, at ~0.9 times the virial radii of both clusters, and two other regions at 1{\deg}and 4{\deg}away from the first pointing. The 4{\deg}-offset observation was used to evaluate the Galactic foreground emission. We did not detect significant redshifted Oxygen emission lines (O VII and O VIII) in the spectra of all three pointings, after subtracting the contribution of foreground and background emission. An upper limit for the redshifted O VIII Ka line intensity of the warm-hot intergalactic medium (WHIM) is 1.5 \times 10^-7 photons s^-1 cm^-2 arcmin^-2, which corresponds to an overdensity of ~380 (Z/0.1 Z_solar)^{-1/2} (L/3 Mpc)^{-1/2}, assuming T=3\times10^6 K. We found excess continuum emission in the 1{\deg}-offset and on-filament regions, represented by thermal models with kT ~1 keV and ~2 keV, respectively. The redshifts of both 0 and that of the supercluster (0.048) are consistent with the observed spectra. The ~1 keV emission can be also fitted with Ne-rich Galactic (zero redshift) thin thermal emission. Radial intensity profile of 2 keV component suggests contribution from A3558 and A3556, but with significant steepening of the intensity slope in the outer region of A3558. Finally, we summarized the previous Suzaku search for the WHIM and discussed the feasibility of constraining the WHIM. An overdensity of < 400 can be detectable using O VII and O VIII emission lines in a range of 1.4\times10^6 K < T < 5\times10^6 K or a continuum emission in a relatively high temperature range T > 5\times10^6 K with the Suzaku XIS. The non detection with Suzaku suggests that typical line-of-sight average overdensity is < 400

Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)

The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Ape1/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Ape1 can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Ape1 redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Ape1. Benzoquinone and naphthoquinone analogues of the Ape1-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Ape1 redox activity, and the most potent analogues inhibited tumor cell growth with IC50 values in the 10−20 μM range

Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung and leukemias, leading to increased aggressiveness. Transcription factors downstream of Ref-1/APE1 are key contributors to many cancers, and Ref-1/APE1 redox signaling inhibition slows growth and progression in a number of tumor types. Ref-1/APE1 inhibition is also highly effective when paired with other drugs, including standard-of-care therapies and therapies targeting pathways affected by Ref-1/APE1 redox signaling. Additionally, Ref-1/APE1 plays a role in a variety of other indications, such as retinopathy, inflammation, and neuropathy. In this review, we discuss the functional consequences of activation of the Ref-1/APE1 node in cancer and other diseases, as well as potential therapies targeting Ref-1/APE1 and related pathways in relevant diseases. APX3330, a novel oral anticancer agent and the first drug to target Ref-1/APE1 for cancer is entering clinical trials and will be explored in various cancers and other diseases bringing bench discoveries to the clinic

Radio Emission from Supernovae

Study of radio supernovae over the past 27 years includes more than three dozen detected objects and more than 150 upper limits. From this work it is possible to identify classes of radio properties, demonstrate conformance to and deviations from existing models, estimate the density and structure of the circumstellar material and, by inference, the evolution of the presupemova stellar wind, and reveal the last stages of stellar evolution before explosion. It is also possible to detect ionized hydrogen along the line of sight, to demonstrate binary properties of the presupemova stellar system, and to detect dumpiness of the circumstellar material. Along with reviewing these general properties of the radio emission from supernovae, we present our extensive observations of the radio emission from supemova (SN) 1993J in M 81 (NGC 3031) made with the Very Large Array and other radio telescopes. The SN 1993J radio emission evolves regularly in both time and frequency, and the usual interpretation in terms of shock interaction with a circumstellar medium (CSM) formed by a pre-supernova stellar wind describes the observations rather well considering the complexity of the phenomenon. However: 1) The highest frequency measurements at 85 - 110 GHz at early times (< 40 days) are not well fitted by the parameterization which describes the cm wavelength measurements rather well. 2) At mid-cm wavelengths there is often deviation from the fitted radio light curves, particularly near the peak flux density, and considerable shorter term deviations in the declining portion when the emission has become optically thin. 3) At a time ~3100 days after shock breakout, the decline rate of the radio emission steepens from (t^(+β))β ~ 0.7 to β ~ —2.7 without change in the spectral index (v^(+α); α ~ -0.81). However, this decline is best described not as a power-law, but as an exponential decay starting at day ~3100 with an e-folding time of ~1100 days. 4) The best overall fit to all of the data is a model including both non-thermal synchrotron self-absorption (SSA) and a thermal free-free absorbing (FFA) components at early times, evolving to a constant spectral index, optically thin decline rate, until a break in that decline rate at day ~3100, as mentioned above. Moreover, neither a purely SSA nor a purely FFA absorbing model can provide a fit that simultaneously reproduces the light curves, the spectral index evolution, and the brightness temperature evolution

Transcriptomic and metabolic responses of Staphylococcus aureus exposed to supra-physiological temperatures

<p>Abstract</p> <p>Background</p> <p>Previous evaluation by different molecular and physiological assays of <it>Staphylococcus aureus </it>(<it>S. aureus</it>) responses to heat shock exposure yielded a still fragmentary view of the mechanisms determining bacterial survival or death at supra-physiological temperatures. This study analyzed diverse facets of <it>S. aureus </it>heat-shock adjustment by recording global transcriptomic and metabolic responses of bacterial cultures shifted for 10 min from 37°C to a sub-lethal (43°C) or eventually lethal (48°C) temperature. A relevant metabolic model of the combined action of specific stress response mechanisms with more general, energy-regulating metabolic pathways in heat-shocked <it>S. aureus </it>is presented.</p> <p>Results</p> <p>While <it>S. aureus </it>cultures shifted to 43°C or left at 37°C showed marginal differences in growth and survival rates, bacterial cultures exposed to 48°C showed a rapid growth arrest followed by a subsequent decline in viable counts. The most substantial heat shock-induced changes at both 43°C and 48°C occurred in transcript levels of HrcA- and CtsR-regulated genes, encoding classical chaperones DnaK and GroESL, and some Hsp100/Clp ATPases components, respectively. Other metabolic pathways up-regulated by <it>S. aureus </it>exposure at 48°C included genes encoding several enzymes coping with oxidative stress, and DNA damage, or/and impaired osmotic balance. Some major components of the pentose phosphate cycle and gluconeogenesis were also up-regulated, which reflected depletion of free glucose by bacterial cultures grown in Mueller-Hinton broth prior to heat shock. In contrast, most purine- and pyrimidine-synthesis pathway components and amino acyl-tRNA synthetases were down-regulated at 48°C, as well as arginine deiminase and major fermentative pathway components, such as alcohol, lactate and formate dehydrogenases. Despite the heat-induced, increased requirements for ATP-dependent macromolecular repair mechanisms combined with declining energy sources, intracellular ATP levels remained remarkably constant during heat shock.</p> <p>Conclusion</p> <p>The sequential loss of replication and viability at 48°C cannot be explained by significant reductions in intracellular ATP levels, but may reflect ATP rerouting for macromolecular repair mechanisms and cell survival. Our metabolic model also suggests that heat-stressed <it>S. aureus </it>should down-regulate the production of potential, DNA-damaging reactive oxygen species that might result from electron transport-generated ATP, involving excessive levels of free heavy metals, in particular iron.</p