The size of the X-ray emitting region in SWIFT J2127.4+5654 via a broad line region cloud X-ray eclipse

We present results obtained from the time-resolved X-ray spectral analysis of the Narrow-Line-Seyfert 1 galaxy SWIFT J2127.4+5654 during a ~130 ks XMM-Newton observation. We reveal large spectral variations, especially during the first ~90 ks of the XMM-Newton exposure. The spectral variability can be attributed to a partial eclipse of the X-ray source by an intervening low-ionization/cold absorbing structure (cloud) with column density N_H = 2.0^{+0.2}_{-0.3}e22 cm^-2 which gradually covers and then uncovers the X-ray emitting region with covering fraction ranging from zero to ~43 per cent. Our analysis enables us to constrain the size, number density, and location of the absorbing cloud with good accuracy. We infer a cloud size (diameter) of $D_c < 1.5e13 cm, corresponding to a density of n_c > 1.5e9 cm^-3 at a distance of R_c > 4.3e16 cm from the central black hole. All of the inferred quantities concur to identify the absorbing structure with one single cloud associated with the broad line region of SWIFT J2127.4+5654. We are also able to constrain the X-ray emitting region size (diameter) to be D_s < 2.3e13 cm which, assuming the black hole mass estimated from single-epoch optical spectroscopy (1.5e7 M_sun), translates into D_s < 10.5 gravitational radii (r_g) with larger sizes (in r_g) being associated with smaller black hole masses, and viceversa. We also confirm the presence of a relativistically distorted reflection component off the inner accretion disc giving rise to a broad relativistic Fe K emission line and small soft excess (small because of the high Galactic column density), supporting the measurement of an intermediate black hole spin in SWIFT J2127.4+5654 that was obtained from a previous Suzaku observation.Comment: 8 pages, 7 figures, accepted for publication in MNRA

The properties of the clumpy torus and BLR in the polar-scattered Seyfert 1 galaxy ESO 323-G77 through X-ray absorption variability

We report results from multi-epoch X-ray observations of the polar-scattered Seyfert 1 galaxy ESO 323-G77. The source exhibits remarkable spectral variability from months to years timescales. The observed spectral variability is entirely due to variations of the column density of a neutral absorber towards the intrinsic nuclear continuum. The column density is generally Compton-thin ranging from a few times 10$^{22}$ cm$^{-2}$ to a few times 10$^{23}$ cm$^{-2}$. However, one observation reveals a Compton-thick state with column density of the order of 1.5 $\times$ 10$^{24}$ cm$^{-2}$. The observed variability offers a rare opportunity to study the properties of the X-ray absorber(s) in an active galaxy. We identify variable X-ray absorption from two different components, namely (i) a clumpy torus whose individual clumps have a density of $\leq$ 1.7 $\times$ 10$^8$ cm$^{-3}$ and an average column density of $\sim$ 4 $\times$ 10$^{22}$ cm$^{-2}$, and (ii) the broad line region (BLR), comprising individual clouds with density of 0.1-8 $\times$ 10$^9$ cm$^{-3}$ and column density of 10$^{23}$-10$^{24}$ cm$^{-2}$. The derived properties of the clumpy torus can also be used to estimate the torus half-opening angle, which is of the order of 47 $^\circ$. We also confirm the previously reported detection of two highly ionized warm absorbers with outflow velocities of 1000-4000 km s$^{-1}$. The observed outflow velocities are consistent with the Keplerian/escape velocity at the BLR. Hence, the warm absorbers may be tentatively identified with the warm/hot inter-cloud medium which ensures that the BLR clouds are in pressure equilibrium with their surroundings. The BLR line-emitting clouds may well be the cold, dense clumps of this outflow, whose warm/hot phase is likely more homogeneous, as suggested by the lack of strong variability of the warm absorber(s) properties during our monitoring.Comment: 15 pages, 4 tables, and 9 figures. Accepted for publication in MNRA

Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology

Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate that N-myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria

Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus

Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections

Eclipsing the innermost accretion disc regions in AGN

Variable X-ray absorption has been observed in active galactic nuclei (AGN) on several time scales. Observations allow us to identify the absorber with clouds associated either with the clumpy torus (parsec scales, long timescales) or with the broad line region (BLR) (short timescales). In the latter, the cloud size has been estimated to be of the order of few gravitational radii from the observed absorption variability. Such small cloud sizes are comparable to the X-ray emitting regions so that a detailed modeling of occultation events in AGN has the potential of enabling us to infer accurately the geometry of the system. We have developed a relativistic X-ray spectral model for occultation events and we present here theoretical predictions on the different observables that can be inferred by studying X-ray eclipses in simulated XMM-Newton data. These include the size of the X-ray emitting regions as well as more fundamental parameters such as the black hole spin and the system inclination. We find that absorption varies as a function of the energy range and that its maximum takes place when the approaching part of the accretion disc is covered. Therefore we study the hard-to-soft (H / S) ratio light curves produced during an eclipse and use them to characterise the properties of the inner accretion disc in a new model-independent way

Spectral and polarimetric signatures of X-ray eclipses in AGNs

International audienceX-ray observations of active galactic nuclei (AGNs) show variability on time-scales ranging from a few hours up to a few days. Some of this variability may be associated with occultation events by clouds in the broad-line region. In this work, we aim to model the spectral and polarization variability arising from X-ray obscuration events, serving as probes of the relativistic effects that dominate the emission from the innermost regions. We show that asymmetries can be clearly detected in the AGNs spectra as the cloud is shading different parts of the accretion disc. We also show that these effects can be detected in the temporal evolution of the polarization degree (P) and the polarization position angle (Ψ). The variations in P and Ψ are highly dependent on the inclination of the system, the position of the primary source and its intrinsic polarization. Considering the disc-corona system only, for an inclination θ = 30° (60°), P increases up to ∼20 per cent (30 per cent) in the 4–8 keV band, when the unpolarized primary source is obscured. However, after accounting for the contribution of parsec-scale material scattering the light in our line of sight (narrow-line region and molecular torus), the variability is smoothed out and the polarization degree can be reduced down to |${\sim } 1{{\ \rm per\ cent}}$| (2 per cent). Our results suggest that the study of eclipses in AGNs with the next generation of X-ray spectral and polarimetric missions could provide unique information on the physics and structure of the innermost regions as well as of the parsec-scale material

Polarimetric view of the changing type Seyfert galaxy ESO 362-G018.

ESO362-G018 is an active galactic nucleus (AGN) which is classified as a Seyfert 1.5 galaxy e.g. by Bennert et al. (2006), (black data set on figure 1). However, Parisi et. al (2009) found an optical spectrum of this source which was taken during the 6dF Galaxy Survey, but it does not show the broad Balmer lines required to classify it as Seyfert 1 galaxy (red data set on figure 1). On the other hand, the results obtained by Agis-Gonzalez et al. (2014❩ in a X-ray analysis of this same source reveal that the inclination of ESO362- G018 i = 53° ± 5° is consistent with the picture of an AGN looked through the upper layers of a clumpy, dusty torus. Thus, according to the Unification Models of AGN and the clumpy nature of the torus, our interpretation of the different spectra is the following one. On 30th of January of 2003 (when the spectrum belonging to the 6dF survey was obtained), our line of sight intercepted a (or several aligned) torus clump(s) with much greater column density than its environment. Accordingly, the nucleus and the broad line region (❨BLR)❩ would be obscured. This allowed only the narrow emission lines to emerge from the narrow line region (NRL). Otherwise, on 18th of September of 2004 (when the spectrum by Bennert et al. 2006 was obtained) there is no clump to intercept and the BLR is not obscured so that the broad Balmer emission lines could be detected

New Ruthenium-Cyclopentadienyl Complexes Affect Colorectal Cancer Hallmarks Showing High Therapeutic Potential

Colorectal cancer (CRC) is among the most deadly cancers worldwide. Current therapeutic strategies have low success rates and several side effects. This relevant clinical problem requires the discovery of new and more effective therapeutic alternatives. Ruthenium drugs have arisen as one of the most promising metallodrugs, due to their high selectivity to cancer cells. In this work we studied, for the first time, the anticancer properties and mechanisms of action of four lead Ru-cyclopentadienyl compounds, namely PMC79, PMC78, LCR134 and LCR220, in two CRC-derived cell lines (SW480 and RKO). Biological assays were performed on these CRC cell lines to evaluate cellular distribution, colony formation, cell cycle, proliferation, apoptosis, and motility, as well as cytoskeleton and mitochondrial alterations. Our results show that all the compounds displayed high bioactivity and selectivity, as shown by low half-maximal inhibitory concentrations (IC50) against CRC cells. We observed that all the Ru compounds have different intracellular distributions. In addition, they inhibit to a high extent the proliferation of CRC cells by decreasing clonogenic ability and inducing cell cycle arrest. PMC79, LCR134, and LCR220 also induce apoptosis, increase the levels of reactive oxygen species, lead to mitochondrial dysfunction, induce actin cytoskeleton alterations, and inhibit cellular motility. A proteomic study revealed that these compounds cause modifications in several cellular proteins associated with the phenotypic alterations observed. Overall, we demonstrate that Ru compounds, especially PMC79 and LCR220, display promising anticancer activity in CRC cells with a high potential to be used as new metallodrugs for CRC therapy

Sistema lipídicos funcionalizados con vinilsulfonas. Síntesis y usos

Número de publicación: ES2337226 B2. Número de solicitud: 200902389.Compuesto que comprende una molécula de naturaleza lipídica y un grupo vinilsulfona que permite llevar a cabo la lipidación de biomoléculas de una forma altamente eficaz y sencilla. La invención también se refiere a sus procedimientos de obtención y a sus usos. Más concretamente se refiere al uso de estos compuestos en el desarrollo de dos nuevas aplicaciones de los ISCOMs basadas en la capacidad de nanoencapsulación y la incorporación de anticuerpos a la membrana de los mismos: a) Su empleo en inmunomarcaje fluorescente; b) Desarrollo de sistemas para el transporte dirigido de fármacos.Universidad de Granad