Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming

Components of the SWI/SNF chromatin remodeling complex, including BRG1 (also SMARCA4), are inactivated in cancer. Among other functions, SWI/SNF orchestrates the response to retinoid acid (RA) and glucocorticoids (GC) involving downregulation of MYC. The epigenetic drugs SAHA and azacytidine, as well as RA and GC, are currently being used to treat some malignancies but their therapeutic potential in lung cancer is not well established. Here we aimed to determine the possible therapeutic effects of azacytidine and SAHA (A/S) alone or in combination with GC plus RA (GC/RA) in lung cancers with either BRG1 inactivation or MYC amplification. In vitro, responses to GC/RA treatment were more effective in MYC-amplified cells. These effects were mediated by BRG1 and involved a reprogramming towards prodifferentiation gene expression signatures and downregulation of MYC. In MYC-amplified cells, administration of GC/RA enhanced the cell growth inhibitory effects of A/S which, in turn, accentuated the prodifferentiation features promoted by GC/RA. Finally, these treatments improved overall survival of mice orthotopically implanted with MYC-amplified, but not BRG1-mutant, cells and reduced tumor cell viability and proliferation. We propose that the combination of epigenetic treatments with retinoids and corticoids of MYC-driven lung tumors constitute a strategy for therapeutic intervention in this otherwise incurable disease

The HELLAS2XMM survey: XI. Unveiling the nature of X-ray Bright Optically Normal Galaxies

X-ray Bright Optically Normal Galaxies (XBONGs) constitute a small but not negligible fraction of hard X-ray selected sources in recent Chandra and XMM-Newton surveys. Even though several possibilities were proposed to explain why a relatively luminous hard X-ray source does not leave any significant signature of its presence in terms of optical emission lines, the nature of XBONGs is still subject of debate. We aim to a better understanding of their nature by means of a multiwavelength and morphological analysis of a small sample of these sources. Good-quality photometric near-infrared data (ISAAC/VLT) of four low-redshift (z=0.1-0.3) XBONGs, selected from the HELLAS2XMM survey, have been used to search for the presence of the putative nucleus, applying the surface-brightness decomposition technique through the least-squares fitting program GALFIT. The surface brightness decomposition allows us to reveal a nuclear point-like source, likely to be responsible of the X-ray emission, in two out of the four sources. The results indicate that moderate amounts of gas and dust, covering a large solid angle (possibly 4pi) at the nuclear source, combined with the low nuclear activity, may explain the lack of optical emission lines. The third XBONG is associated with an X-ray extended source and no nuclear excess is detected in the near infrared at the limits of our observations. The last source is associated to a close (d< 1 arcsec) double system and the fitting procedure cannot achieve a firm conclusion.Comment: 20 pages, 12 figures, A&A in pres

AEGIS: Demographics of X-ray and Optically Selected AGNs

We develop a new diagnostic method to classify galaxies into AGN hosts, star-forming galaxies, and absorption-dominated galaxies by combining the [O III]/Hbeta ratio with rest-frame U-B color. This can be used to robustly select AGNs in galaxy samples at intermediate redshifts (z<1). We compare the result of this optical AGN selection with X-ray selection using a sample of 3150 galaxies with 0.3<z<0.8 and I_AB<22, selected from the DEEP2 Galaxy Redshift Survey and the All-wavelength Extended Groth Strip International Survey (AEGIS). Among the 146 X-ray sources in this sample, 58% are classified optically as emission-line AGNs, the rest as star-forming galaxies or absorption-dominated galaxies. The latter are also known as "X-ray bright, optically normal galaxies" (XBONGs). Analysis of the relationship between optical emission lines and X-ray properties shows that the completeness of optical AGN selection suffers from dependence on the star formation rate and the quality of observed spectra. It also shows that XBONGs do not appear to be a physically distinct population from other X-ray detected, emission-line AGNs. On the other hand, X-ray AGN selection also has strong bias. About 2/3 of all emission-line AGNs at L_bol>10^44 erg/s in our sample are not detected in our 200 ks Chandra images, most likely due to moderate or heavy absorption by gas near the AGN. The 2--7 keV detection rate of Seyfert 2s at z~0.6 suggests that their column density distribution and Compton-thick fraction are similar to that of local Seyferts. Multiple sample selection techniques are needed to obtain as complete a sample as possible.Comment: 24 pages, 14 figures, submitted to ApJ. Version 2 matches the ApJ accepted version. Sec 3 was reorganized and partly rewritten with one additional figure (Fig.3

The Nature of Optically Dull Active Galactic Nuclei in COSMOS

We present infrared, optical, and X-ray data of 48 X-ray bright, optically dull AGNs in the COSMOS field. These objects exhibit the X-ray luminosity of an active galactic nucleus (AGN) but lack broad and narrow emission lines in their optical spectrum. We show that despite the lack of optical emission lines, most of these optically dull AGNs are not well-described by a typical passive red galaxy spectrum: instead they exhibit weak but significant blue emission like an unobscured AGN. Photometric observations over several years additionally show significant variability in the blue emission of four optically dull AGNs. The nature of the blue and infrared emission suggest that the optically inactive appearance of these AGNs cannot be caused by obscuration intrinsic to the AGNs. Instead, up to ~70% of optically dull AGNs are diluted by their hosts, with bright or simply edge-on hosts lying preferentially within the spectroscopic aperture. The remaining ~30% of optically dull AGNs have anomalously high f_x/f_o ratios and are intrinsically weak, not obscured, in the optical. These optically dull AGNs are best described as a weakly accreting AGN with a truncated accretion disk from a radiatively inefficient accretion flow.Comment: 12 pages, 10 figures. Accepted for publication in the Ap

Evolution of the Early-Type Galaxy Fraction in Clusters since z = 0.8

We study the morphological content of a large sample of high-redshift clusters to determine its dependence on cluster mass and redshift. Quantitative morphologies are based on bulge+disk decompositions of cluster and field galaxies on deep VLT/FORS2 images of 18 optically-selected clusters at 0.45 < z < 0.80 from the ESO Distant Cluster Survey (EDisCS). Morphological content is given by the early-type galaxy fraction f_et, and early-type galaxies are selected based on their bulge fraction and image smoothness. A set of 158 SDSS clusters is analyzed exactly as the EDisCS sample to provide a robust local comparison. Our main results are: (1) f_et values for the SDSS and EDisCS clusters exhibit no clear trend as a function of sigma. (2) Mid-z EDisCS clusters around sigma = 500 km/s have f_et ~= 0.5 whereas high-z EDisCS clusters have f_et ~= 0.4 (~25% increase over 2 Gyrs). (3) There is a marked difference in the morphological content of EDisCS and SDSS clusters. None of the EDisCS clusters have f_et greater than 0.6 whereas half of the SDSS clusters lie above this value. This difference is seen in clusters of all velocity dispersions. (4) There is a strong correlation between morphology and star formation in SDSS and EDisCS clusters. This correlation holds independent of sigma and z even though the fraction of [OII] emitters decreases from z~0.8 to z~0.06 in all environments. Our results pose an interesting challenge to structural transformation and star formation quenching processes that strongly depend on the global cluster environment and suggest that cluster membership may be of lesser importance than other variables in determining galaxy properties. (ABRIDGED)Comment: 22 pages, 10 figures, accepted for publication in A&

Parsec-scale dust emission from the polar region in the type 2 nucleus of NGC 424

Advancements in infrared IR open up the possibility to spatially resolve AGN on the parsec-scale level and study the circumnuclear dust distribution, commonly referred to as the "dust torus", that is held responsible for the type 1/type 2 dichotomy of AGN. We used the mid-IR beam combiner MIDI together with the 8m telescopes at the VLTI to observe the nucleus of the Seyfert 2 galaxy NGC 424, achieving an almost complete coverage of the uv-plane accessible by the available telescope configurations. We detect extended mid-IR emission with a relatively baseline- and model-independent mid-IR half-light radius of (2.0 \pm 0.2) pc \times (1.5 \pm 0.3) pc (averaged over the 8-13 {\mu}m wavelength range). The extended mid-IR source shows an increasing size with wavelength. The orientation of the major axis in position angle -27deg is closely aligned with the system axis as set by optical polarization observations. Torus models typically favor extension along the mid-plane at mid-IR wavelengths instead. Therefore, we conclude that the majority of the pc-scale mid-IR emission (>~60%) in this type 2 AGN originates from optically-thin dust in the polar region of the AGN, a scenario consistent with the near- to far-IR SED. We suggest that a radiatively-driven dusty wind, possibly launched in a puffed-up region of the inner hot part of the torus, is responsible for the polar dust. In this picture, the torus dominates the near-IR emission up to about 5 {\mu}m, while the polar dust is the main contributor to the mid-IR flux. Our results of NGC 424 are consistent with recent observations of the AGN in the Circinus galaxy and resemble large-scale characteristics of other objects. If our results reflect a general property of the AGN population, the current paradigm for interpreting and modeling the IR emission of AGN have to be revised. (abridged)Comment: 18 pages, 10 figures, 4 tables; accepted by ApJ (June 20

Demystifying the coronal line region of active galactic nuclei: spatially resolved spectroscopy with HST

We present an analysis of STIS/HST optical spectra of a sample of ten Seyfert galaxies aimed at studying the structure and physical properties of the coronal-line region (CLR). The high-spatial resolution provided by STIS allowed us to resolve the CLR and obtain key information about the kinematics of the coronal-line gas, measure directly its spatial scale, and study the mechanisms that drive the high-ionisation lines. We find CLRs extending from just a few parsecs (~10 pc) up to 230 pc in radius, consistent with the bulk of the coronal lines (CLs) originating between the BLR and NLR, and extending into the NLR in the case of [FeVII] and [NeV] lines. The CL profiles strongly vary with the distance to the nucleus. We observed line splitting in the core of some of the galaxies. Line peak shifts, both red- and blue-shifts, typically reached 500 km/s, and even higher velocities (1000 km/s) in some of the galaxies. In general, CLs follow the same pattern of rotation curves as low-ionisation lines like [OIII]. From a direct comparison between the radio and the CL emission we find that neither the strength nor the kinematics of the CLs scale in any obvious and strong way with the radio jets. Moreover, the similarity of the flux distributions and kinematics of the CLs and low-ionisation lines, the low temperatures derived for the gas, and the success of photoionisation models to reproduce, within a factor of few, the observed line ratios, point towards photoionisation as the main driving mechanism of CLs.Comment: Accepted for publication in MNRAS. 27 pages, 21 figures, 4 table

Is IRAS 01072+4954 a True-Seyfert 2? Hints from Near Infrared Integral Field Spectroscopy

In contrast to the predictions of the unified model, some X-ray unobscured Seyfert 2 galaxies have been discovered in the last decade. One of them, the starburst/Seyfert composite galaxy IRAS 01072+4954 (z=0.0236), has a typical Type~1 X-ray emission, while its optical spectrum resembles an HII galaxy and lacks the expected broad lines. We performed near-infrared integral-field observations of this object with the aim to determine the nature of its nuclear emission and to find indications for the existence or absence of a broad-line region. Several reasons have been proposed to explain such peculiar emission. We studied the validity of such hypotheses, including the possibility for it to be True-Seyfert~2. We found little obscuration towards the nucleus A_V = 2.5 mag, and a nuclear star-formation rate Sigma_SFR < 11.6 Msun yr^{-1} kpc^{-2}, which is below the average in Seyferts. Unresolved hot-dust emission with T ~ 1150 K seems to indicate the presence of a torus with its axis close to the line of sight. We found that IRAS 01072+4954 hosts a low mass black hole with an estimated mass of M_BH ~ 10^5 Msun and an upper limit of 2.5x10^6 Msun. Its bolometric luminosity is L_bol ~ 2.5x10^{42} erg/s, which yields a high accretion rate with an Eddington ratio ~ 0.2. If the relations found in more massive systems also apply to this case, then IRAS 01072+4954 should show broad emission lines with FWHM_{broad} ~(400-600) km/s. Indeed, some indications for such narrow broad-line components are seen in our data, but the evidence is not yet conclusive. This source thus seems not to be a True-Seyfert 2, but an extreme case of a narrow line Seyfert 1, which, due to the faintness of the active nucleus, does not have strong FeII emission in the optical.Comment: 16 pages, 11 figures. A&A Accepted versio

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Differential branching fraction and angular analysis of the decay B0→K∗0μ+μ−

The angular distribution and differential branching fraction of the decay B 0→ K ∗0 μ + μ − are studied using a data sample, collected by the LHCb experiment in pp collisions at s√=7 TeV, corresponding to an integrated luminosity of 1.0 fb−1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions