YB-1 dependent oncolytic adenovirus efficiently inhibits tumor growth of glioma cancer stem like cells

Background: The brain cancer stem cell (CSC) model describes a small subset of glioma cells as being responsible for tumor initiation, conferring therapy resistance and tumor recurrence. In brain CSC, the PI3-K/AKT and the RAS/mitogen activated protein kinase (MAPK) pathways are found to be activated. In consequence, the human transcription factor YB-1, knowing to be responsible for the emergence of drug resistance and driving adenoviral replication, is phosphorylated and activated. With this knowledge, YB-1 was established in the past as a biomarker for disease progression and prognosis. This study determines the expression of YB-1 in glioblastoma (GBM) specimen in vivo and in brain CSC lines. In addition, the capacity of Ad-Delo3-RGD, an YB-1 dependent oncolytic adenovirus, to eradicate CSC was evaluated both in vitro and in vivo. Methods: YB-1 expression was investigated by immunoblot and immuno-histochemistry. In vitro, viral replication as well as the capacity of Ad-Delo3-RGD to replicate in and, in consequence, to kill CSC was determined by real-time PCR and clonogenic dilution assays. In vivo, Ad-Delo3-RGD-mediated tumor growth inhibition was evaluated in an orthotopic mouse GBM model. Safety and specificity of Ad-Delo3-RGD were investigated in immortalized human astrocytes and by siRNA-mediated downregulation of YB-1. Results: YB-1 is highly expressed in brain CSC lines and in GBM specimen. Efficient viral replication in and virus-mediated lysis of CSC was observed in vitro. Experiments addressing safety aspects of Ad-Delo3-RGD showed that (i) virus production in human astrocytes was significantly reduced compared to wild type adenovirus (Ad-WT) and (ii) knockdown of YB-1 significantly reduced virus replication. Mice harboring othotopic GBM developed from a temozolomide (TMZ)-resistant GBM derived CSC line which was intratumorally injected with Ad-Delo3-RGD survived significantly longer than mice receiving PBS-injections or TMZ treatment. Conclusion: The results of this study supported YB-1 based virotherapy as an attractive therapeutic strategy for GBM treatment which will be exploited further in multimodal treatment concepts

Type IIn Supernova SN 2010jl: Optical Observations for Over 500 Days After Explosion

We present extensive optical observations of a Type IIn supernova (SN) 2010jl for the first 1.5 years after the discovery. The UBVRI light curves demonstrated an interesting two-stage evolution during the nebular phase, which almost flatten out after about 90 days from the optical maximum. SN 2010jl has one of the highest intrinsic H_alpha luminosity ever recorded for a SN IIn, especially at late phase, suggesting a strong interaction of SN ejecta with the dense circumstellar material (CSM) ejected by the progenitor. This is also indicated by the remarkably strong Balmer lines persisting in the optical spectra. One interesting spectral evolution about SN 2010jl is the appearance of asymmetry of the Balmer lines. These lines can be well decomposed into a narrow component and an intermediate-width component. The intermediate-width component showed a steady increase in both strength and blueshift with time until t ~ 400 days after maximum, but it became less blueshifted at t ~ 500 days when the line profile appeared relatively symmetric again. Owing to that a pure reddening effect will lead to a sudden decline of the light curves and a progressive blueshift of the spectral lines, we therefore propose that the asymmetric profiles of H lines seen in SN 2010jl is unlikely due to the extinction by newly formed dust inside the ejecta, contrary to the explanation by some early studies. Based on a simple CSM-interaction model, we speculate that the progenitor of SN 2010jl may suffer a gigantic mass loss (~ 30-50 M_sun) in a few decades before explosion. Considering a slow moving stellar wind (e.g., ~ 28 km/s) inferred for the preexisting, dense CSM shell and the extremely high mass-loss rate (1-2 M_sun per yr), we suggest that the progenitor of SN 2010jl might have experienced a red supergiant stage and explode finally as a post-red supergiant star with an initial mass above 30-40 M_sun.Comment: 34 pages, 9 figures, accepted for publication in A

Combined geochemical and electrochemical methodology to quantify corrosion of carbon steel by bacterial activity.

International audienceThe availability of respiratory substrates, such as H2 and Fe(II,III) solid corrosion products within nuclear waste repository, will sustain the activities of hydrogen-oxidizing bacteria (HOB) and iron-reducing bacteria (IRB). This may have a direct effect on the rate of carbon steel corrosion. This study investigates the effects of Shewanella oneidensis (an HOB and IRB model organism) on the corrosion rate by looking at carbon steel dissolution in the presence of H2 as the sole electron donor. Bacterial effect is evaluated by means of geochemical and electrochemical techniques. Both showed that the corrosion rate is enhanced by a factor of 2-3 in the presence of bacteria. The geochemical experiments indicated that the composition and crystallinity of the solid corrosion products (magnetite and vivianite) are modified by bacteria. Moreover, the electrochemical experiments evidenced that the bacterial activity can be stimulated when H2 is generated in a small confinement volume. In this case, a higher corrosion rate and mineralization (vivianite) on the carbon steel surface were observed. The results suggest that the mechanism likely to influence the corrosion rate is the bioreduction of Fe(III) from magnetite coupled to the H2 oxidation

Optical multiband surface photometry of a sample of Seyfert galaxies. III. Global, isophotal, and bar parameters

This paper is third in a series, studying the optical properties of a sample of Seyfert galaxies. Here we present a homogeneous set of global (ellipticity, position angle, inclination, and total magnitude) and isophotal (semi-major axis and colour indices at 24 V mag/sq.arcsec) parameters of the galaxy sample. We find the following median corrected isophotal colour indices: B-Ic = 1.9 mag/sq.arcsec and V-Ic = 1.1 mag/sq.arcsec. A set of bar parameters - ellipticity, position angle, semi-major axis corresponding to the ellipticity maximum in the bar region, and length, are also reported; deprojection has been applied to the bar ellipticity, length, and relative length in terms of galaxy isophotal semi-major axis. Regarding bar length estimation, we use a method, based on the relation between the behaviour of the profiles and orbit analysis. The so estimated bar length tightly correlates with the semi-major axis, corresponding to the ellipticity maximum with a median ratio of the former to the latter of 1.22. The median of the deprojected bar ellipticity, length, and relative length are 0.39, 5.44 kpc, and 0.44, respectively. There is a correlation between the deprojected bar length and the corrected isophotal semi-major axis at 24 V mag/sq.arcsec. Three of the 17 large-scale bars appear strong, based on the deprojected bar ellipticity as a first-order approximation of bar strength. The deprojected relative bar length does not appear to correlate with the bar ellipticity.Comment: AN, in pres

Amplitudes and lifetimes of solar-like oscillations observed by CoRoT* Red-giant versus main-sequence stars

Context. The advent of space-borne missions such as CoRoT or Kepler providing photometric data has brought new possibilities for asteroseismology across the H-R diagram. Solar-like oscillations are now observed in many stars, including red giants and main- sequence stars. Aims. Based on several hundred identified pulsating red giants, we aim to characterize their oscillation amplitudes and widths. These observables are compared with those of main-sequence stars in order to test trends and scaling laws for these parameters for both main-sequence stars and red giants. Methods. An automated fitting procedure is used to analyze several hundred Fourier spectra. For each star, a modeled spectrum is fitted to the observed oscillation spectrum, and mode parameters are derived. Results. Amplitudes and widths of red-giant solar-like oscillations are estimated for several hundred modes of oscillation. Amplitudes are relatively high (several hundred ppm) and widths relatively small (very few tenths of a {\mu}Hz). Conclusions. Widths measured in main-sequence stars show a different variation with the effective temperature than red giants. A single scaling law is derived for mode amplitudes of both red giants and main-sequence stars versus their luminosity to mass ratio. However, our results suggest that two regimes may also be compatible with the observations.Comment: Accepted in A&A on 2011 February 8th, now includes corrections (results now more precise on \Gamma and A_max in Section 4.3 and 4.4, fig. 7 corrected consequently

Intermittent Surface Oxygenation Results in Similar Mitochondrial Protection and Maintenance of Aerobic Metabolism as Compared to Continuous Oxygenation during Hypothermic Machine Kidney Machine Perfusion

Short bubble and subsequent surface oxygenation is an innovative oxygenation technique and alternative for membrane oxygenation during hypothermic machine perfusion (HMP). The metabolic effect of the interruption of surface oxygenation for 4 h (mimicking organ transport) during HMP was compared to continuous surface and membrane oxygenation in a pig kidney ex situ preservation model. After 30 min of warm ischemia by vascular clamping, a kidney of a ±40 kg pig was procured and subsequently preserved according to one of the following groups: (1) 22-h HMP + intermittent surface oxygenation ( = 12); (2) 22-h HMP + continuous membrane oxygenation ( = 6); and (3) 22-h HMP + continuous surface oxygenation ( = 7). Brief perfusate O uploading before kidney perfusion was either obtained by direct bubble (groups 1, 3) or by membrane (group 2) oxygenation. Bubble oxygenation during minimum 15 min was as efficient as membrane oxygenation in achieving supraphysiological perfusate pO levels before kidney perfusion. Metabolic tissue analysis (i.e., lactate, succinate, ATP, NADH, and FMN) during and at the end of the preservation period demonstrated similar mitochondrial protection between all study groups. Short bubble and subsequent intermittent surface oxygenation of the perfusate of an HMP-kidney might be an effective and cheap preservation strategy to protect mitochondria, eliminating the need/costs of a membrane oxygenator and oxygen source during transport

4U 1344-60: a bright intermediate Seyfert galaxy at z=0.012 with a relativistic Fe Kalpha emission line

We present analysis of the optical and X-ray spectra of the low Galactic latitude bright (F(2-10) = 3.6 10^{-11} erg/cm2/s) source 4U 1344-60. On the basis of the optical data we propose to classify 4U 1344-60 as an intermediate type Seyfert galaxy and we measure a value of z=0.012+/-0.001 for its redshift. From the XMM-Newton observation we find that the overall X-ray spectral shape of 4U 1344-60 is complex and can be described by a power-law continuum (Gamma ~ 1.55) obscured by two neutral absorption components (Nh(f) ~ 10^{22} cm^{-2} and Nh(p) ~ 4 10^{22} cm^{-2}), the latter covering only the ~50% of the primary X-ray source. The X-ray data therefore lend support to our classification of 4U 1344-60. It exhibits a broad and skewed Fe Kalpha line at 6.4 keV, which suggests the existence of an accretion disk that is able to reprocess the primary continuum down to a few gravitational radii. Such a line represents one of the clearest examples of a relativistic line observed by XMM-Newton so far. Our analysis has also revealed the marginal presence of two narrow line-like emission features at ~4.9 and ~5.2 keV.Comment: Accepted for publication in Astronomy & Astrophysic