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Shprintzen-Goldberg syndrome (SGS) is a rare systemic connective tissue disorder characterized by craniofacial, skeletal, neurodevelopmental, cutaneous, and cardiovascular manifestations, including aortic root aneurysm. It has significant phenotypic overlap with both Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). We previously reported that SGS is caused by heterozygous mutations in the Sloan-Kettering Institute proto-oncogene (SKI), which encodes a potent suppressor of transforming growth factor beta (TGFβ) target gene expression. Herein, we show that mouse lines harboring orthologous amino acid substitutions inSkirecapitulate multiple human SGS phenotypic manifestations, including skin collagen deposition, skeletal kyphosis, behavioral hypoactivity, and aortic root aneurysm. Furthermore, aortic root aneurysm in SGS mice is associated with both increased acetylation of histone H3 at lysine-27 (H3K27) and TGFβ target gene expression, all of which can be ameliorated by pharmacological CBP/P300 inhibition in vivo; similar findings were seen in cultured dermal fibroblast from SGS patients. Aortic root growth is also abrogated in a mouse model of MFS by selective CBP/P300 inhibition in association with blunted expression of TGFβ target genes. These data document excessive H3K27 acetylation and hence TGFβ target gene expression in the pathogenesis of inherited presentations of aortic root aneurysm and the therapeutic potential of pharmacological epigenetic modulation.

espanolResumen Introduccion: este trabajo reconoce las criticas que hacen algunos estudios a las maneras como la Educacion se ha ocupado del cuerpo en contextos de aula: cuerpos fijos, inmoviles, silenciosos y normalizados; frente a la vision de la educacion moderna que se dirige hacia lo razonable y estrecha lo sensible, la pregunta por los rastros corpograficos no trata unicamente de poner el cuerpo en la Educacion, sino de pensar como se hace y que se hace con los cuerpos en contextos de aula universitaria. Objetivo: identificar los rastros corpograficos o las maneras como se le da la "palabra" al cuerpo en el aula a partir de la experiencia de ensenar en contextos de aula universitaria. Materiales y metodos: se trata de una investigacion educativa con metodo rizomatico (rhizoanalytic). El trabajo empirico privilegio la observacion de la escena o el encuentro pedagogico (la clase), la entrevista y el analisis documental de materiales propios de las clases. Resultados: los rastros corpograficos que surgen de la experiencia de ensenar en contextos de aula universitaria dan cuenta de dos dimensiones: la primera, anuncia la idea de Aula viva cuando los cuerpos se hacen presentes: Corpo-Sonoridades; Corpo-Biografias; Corpo-Geografias de la piel y una Corpografia motriz. La segunda dimension indica la germinacion de un plano de composicion para una Educacion Corporal: "Pedagogias que elogian la lentitud", "Pedagogias del tacto", Pedagogias que anuncian un saber de si", "Pedagogias de la experiencia" y "Pedagogias de la presencia". Conclusiones: En estas experiencias de aula universitaria encontramos nuevas relaciones entre los cuerpos y la educacion mas alla de la perspectiva disciplinaria que arraiga el adiestramiento con la idea de ocultar el sujeto de su cuerpo. Analizar las formas como se "grafian" los cuerpos en el aula vuelve movediza la didactica, porque pensar desde el cuerpo exige habitar el aula con pedagogias "encarnadas" que resultan reveladoras para un pensar "corporal" y estimular la creacion de unas didacticas-otras o heterodidacticas. EnglishAbstract Introduction: this work recognises the criticisms that some studies make of how Education has dealt with the body in classroom contexts: fixed, immobile, silent and standardised bodies; against the vision of modern education that is directed towards the reasonable and narrows the sensible, the question about the "corpographic" traces is not only about putting the body in Education but about thinking about how it is done and what is done with those bodies in university classroom contexts. Objective: identify the "corpographic" traces or the ways in which the "word" is given to the body in the classroom based on the experience of teaching in university classroom contexts. Materials and methods: it is an educational research with rhizomatic method (rhizoanalytic). The empirical work privileged the observation of the scene or the pedagogical encounter (the class), the interview and the documentary analysis of typical classroom material. Results: the "corpographic" traces that emerge from the experience of teaching in university classroom contexts account for two dimensions: the first one announces the idea of a living classroom when bodies are present: Body-Sonorities; Body-Biographies; Body-Geographies of the skin and a motor "corpography". The second dimension indicates the germination of a composition plane for a "Corporal Education": "Pedagogies that praise the slowness", "Pedagogies of touch", Pedagogies that announce a knowledge of oneself "," Pedagogies of experience "and" Pedagogies of the presence". Conclusions: in these university classroom experiences, we find new relationships between bodies and education beyond the disciplinary perspective that roots the training with the idea of hiding the subject of your body. Analysing the ways in which bodies are written in the classroom makes didactics changeable because thinking from the body requires inhabiting the classroom with "embodied" pedagogies that are revealing for "corporal" thinking and stimulate the creation of another-didactic or "heterodidactics". portuguesResumo Introducao: Este trabalho reconhece as criticas que alguns estudos fazem as maneiras como a Educacao vem se ocupando do corpo nos contextos de sala de aula: corpos fixos, imoveis, silenciosos e padronizados; frente a visao da educacao moderna que se volta para o racional e reduz o sensivel, la pergunta pelos rastros corpograficos nao trata unicamente de colocar o corpo na Educacao, mas de pensar como se faz e o que se faz com os corpos em contextos de salas de aula universitaria. Objetivo: identificar os rastros corpograficos ou as maneiras como se da a "palavra" ao corpo na aula a partir da experiencia de ensinar em contextos de sala de aula universitaria. Materiais e Metodos: Trata-se de uma investigacao educativa com metodo rizomatico (rhizoanalytic). O trabalho empirico privilegiou a observacao do ambiente ou do encontro pedagogico (a sala de aula), a entrevista e a analise documental de materiais proprios das aulas. Resultados: os rastros corpograficos que surgem da experiencia de ensinar em contextos de sala de aula universitaria dao conta de duas dimensoes: a primeira anuncia a ideia de Aula Viva, quando os corpos se fazem presente: Corpo-Sonoridades; Corpo-Biografias; Corpo-Geografia da pele e uma Corpografia motriz. A segunda dimensao indica a germinacao de um plano de composicao para uma Educacao Corporal: "Pedagogias que elogiam a lentidao", "Pedagogias do Tato", "Pedagogias que anunciam um saber de si", "Pedagogias da experiencia" e "Pedagogias da presenca". Conclusoes: nestas experiencias de aulas universitarias encontramos novas relacoes entre os corpos e a educacao, alem da perspectiva disciplinar que aprofunda o adestramento com a ideia de ocultar o sujeito de seu corpo. Analisar as formas como se "grafiam" os corpos em aula torna maleavel a didatica, porque pensar a partir do corpo exige habitar a aula com pedagogias "encarnadas" que resultam reveladoras para um "pensar corporal" e estimular a criacao de umas "didaticas-outras" ou "heterodidaticas".

We present a definitive assessment of the role of Inverse Compton scattering of Cosmic Microwave Background photons (IC/CMB) in the context of radio galaxies. Owing to the steep increase of the CMB radiation energy density, IC/CMB is supposed to become progressively more important with respect to radio synchrotron cooling as the redshift increases. For typical energies at play, this process will up-scatter the CMB photons into the X-ray band, and is thus expected to yield a redshift-dependent, concurrent X-ray brightening and radio dimming of the jet-powered structures. Here we show how a conclusive proof of this effect hinges on high-resolution imaging data in which the extended lobes can be distinguished from the compact hot spots where synchrotron-self-Compton dominates the X-ray emission regardless of redshift. We analyze Chandra and Very Large Array data of 11 radio galaxies between 1.33 radio galaxies below, Comment: 16 pages, 5 figures, 5 tables. Accepted for publication in MNRAS

We present a sample of intermediate-mass black hole (IMBH) candidates based on the detection of a broad H$\alpha$ emission line and variability, which are selected from the Sloan Digital Sky Survey Data Release 7. By performing spectral decomposition of emission lines as well as visual inspection, we initially identified 131 targets with a broad H$\alpha$ line among a large sample of emission-line galaxies. We further selected 25 IMBH candidates, whose estimated black hole mass (M$_{\rm BH}$) is less than $10^6 \rm M_{\odot}$. To constrain the nature of these candidates, we analyzed X-ray properties and performed an intra-night variability monitoring with optical telescopes. Based on the optical variability analysis, we report a sample of 11 targets with detected intra-night variability as the best IMBH candidates, which are suitable for follow-up observations for accurate M$_{\rm BH}$ determination such as reverberation mapping campaigns., Comment: Accepted for publication in AJ (Dec. 4th, 2021). 24 pages, 7 figures

Black hole X-ray binaries in the quiescent state (Eddington ratios typically $\lesssim$10$^{-5}$) display softer X-ray spectra (photon indices $\Gamma\sim2$) compared to higher-luminosity black hole X-ray binaries in the hard state ($\Gamma\sim1.7$). However, the cause of this softening, and its implications for the underlying accretion flow, are still uncertain. Here, we present quasi-simultaneous X-ray and radio spectral monitoring of the black hole X-ray binary MAXI J1820$+$070 during the decay of its 2018 outburst and of a subsequent re-flare in 2019, providing an opportunity to monitor a black hole X-ray binary as it actively transitions into quiescence. We probe 1-10 keV X-ray luminosities as low as $L_{\rm X}\sim4\times10^{32}$ erg s$^{-1}$, equivalent to Eddington fractions of $\sim4\times10^{-7}$. During its decay towards quiescence, the X-ray spectrum of MAXI J1820$+$070 softens from $\Gamma\sim1.7$ to $\Gamma\sim2$, with the softening taking $\sim30$d, and completing at $L_{\rm X}\approx10^{34}$ erg s$^{-1}$ ($\approx10^{-5} L_{\rm Edd}$). While the X-ray spectrum softens, the radio spectrum generally remains flat/inverted throughout the decay. We also find that MAXI J1820$+$070 follows a radio ($L_{\rm R}$) -- X-ray luminosity correlation of the form $L_{\rm R} \propto L_{\rm X}^{0.52\pm0.07}$, making it the fourth black hole system to follow the so-called `standard track' unbroken over several (in this case, four) decades in $L_{\rm X}$. Comparing the radio/X-ray spectral evolution(s) with the $L_{\rm R}$ -- $L_{\rm X}$ plane, we find that the X-ray softening is consistent with X-rays produced by Comptonization processes in a radiatively inefficient accretion flow. We generally disfavor X-ray emission originating solely from within the jet, with the possible exception of X-rays produced via synchrotron self-Compton processes., Comment: 19 pages, 5 figure, 1 appendix. Accepted for publication in ApJ

We present ultraviolet spectroscopy covering the Lyα + N v complex of six candidate low-redshift (0.9 < z < 1.5) weak emission-line quasars (WLQs) based on observations with the Hubble Space Telescope. The original systematic searches for these puzzling Type 1 quasars with intrinsically weak broad emission lines revealed an N ≈ 100 WLQ population from optical spectroscopy of high-redshift (z > 3) quasars, defined by a Lyα + N v rest-frame equivalent width (EW) threshold z < 3) WLQ candidates, however, has relied primarily on optical spectroscopy of weak broad emission lines at longer rest-frame wavelengths. With these new observations expanding existing optical coverage into the ultraviolet, we explore unifying the low- and high-z WLQ populations via EW[Lyα+N v]. Two objects in the sample unify with high-z WLQs, three others appear consistent with the intermediate portion of the population connecting WLQs and normal quasars, and the final object is consistent with typical quasars. The expanded wavelength coverage improves the number of available line diagnostics for our individual targets, allowing a better understanding of the shapes of their ionizing continua. The ratio of EW[Lyα+N v] to EW[Mg ii] in our sample is generally small but varied, favoring a soft ionizing continuum scenario for WLQs, and we find a lack of correlation between EW[Lyα+N v] and the X-ray properties of our targets, consistent with a “slim-disk” shielding gas model. We also find indications that weak absorption may be a more significant contaminant in low-z WLQ populations than previously thought.

Many ultra-diffuse galaxies (UDGs) have been discovered in the Coma cluster, and there is evidence that some, notably Dragonfly 44, have Milky Way-like dynamical masses despite dwarf-like stellar masses. We used X-ray, UV, and optical data to investigate the star formation and nuclear activity in the Coma UDGs, and we obtained deep UV and X-ray data (Swift and XMM-Newton) for Dragonfly 44 to search for low-level star formation, hot circumgalactic gas, and the integrated emission from X-ray binaries. Among the Coma UDGs, we find UV luminosities consistent with quiescence but NUV$-r$ colors indicating star formation in the past Gyr. This indicates that the UDGs were recently quenched. The $r$-band luminosity declines with projected distance from the Coma core. The Dragonfly 44 UV luminosity is also consistent with quiescence, with SFR$ 10^8 M_{\odot}$ within the virial radius, which would normally be expected for a dynamically massive galaxy. The absence of bright, low mass X-ray binaries is consistent with the expectation from the galaxy total stellar mass, but it is unlikely if most low-mass X-ray binaries form in globular clusters, as Dragonfly 44 has a very large population. Based on the UV and X-ray analysis, the Coma UDGs are consistent with quenched dwarf galaxies, although we cannot rule out a dynamically massive population., 12 pages, 5 tables, 7 figures. Accepted for publication in MNRAS

About half of nearby galaxies have a central surface brightness >1 magnitude below that of the sky. The overall properties of these low-surface-brightness galaxies (LSBGs) remain understudied, and in particular we know very little about their massive black hole population. This gap must be closed to determine the frequency of massive black holes at z=0 as well as to understand their role in regulating galaxy evolution. Here we investigate the incidence and intensity of nuclear, accretion-powered X-ray emission in a sample of 32 nearby LSBGs with the Chandra X-ray Observatory. A nuclear X-ray source is detected in 4 galaxies (12.5%). Based on an X-ray binary contamination assessment technique developed for normal galaxies, we conclude that the detected X-ray nuclei indicate low-level accretion from massive black holes. The active fraction is consistent with that expected from the stellar mass distribution of the LSBGs, but not their total baryonic mass, when using a scaling relation from an unbiased X-ray survey of normal galaxies. This suggests that their black holes co-evolved with their stellar population. In addition, the apparent agreement nearly doubles the number of galaxies available within ~100 Mpc for which a measurement of nuclear activity can efficiently constrain the frequency of black holes as a function of stellar mass. We conclude by discussing the feasibility of measuring this occupation fraction to a few percent precision below 1e10 solar masses with high-resolution, wide-field X-ray missions currently under consideration., 17 pages, accepted by ApJ

Exoplanets residing close to their stars can experience evolution of both their physical structures and their orbits due to the influence of their host stars. In this work, we present a coupled analysis of dynamical tidal dissipation and atmospheric mass loss for exoplanets in XUV irradiated environments. As our primary application, we use this model to study the TRAPPIST-1 system, and place constraints on the interior structure and orbital evolution of the planets. We start by reporting on a UV continuum flux measurement (centered around $\sim1900$ Angstroms) for the star TRAPPIST-1, based on 300 ks of Neil Gehrels Swift Observatory data, and which enables an estimate of the XUV-driven thermal escape arising from XUV photo-dissociation for each planet. We find that the X-ray flaring luminosity, measured from our X-ray detections, of TRAPPIST-1 is 5.6 $\times$10$^{-4} L_{*}$, while the full flux including non-flaring periods is 6.1 $\times$10$^{-5} L_{*}$, when $L_{*}$ is TRAPPIST-1's bolometric luminosity. We then construct a model that includes both atmospheric mass-loss and tidal evolution, and requires the planets to attain their present-day orbital elements during this coupled evolution. We use this model to constrain the ratio $Q'=3Q/2k_{2}$ for each planet. Finally, we use additional numerical models implemented with the Virtual Planet Simulator \texttt{VPLanet} to study ocean retention for these planets using our derived system parameters., Comment: accepted to AJ. See extra figures, data, and scripts at https://github.com/jxcbecker/trappist1

The black hole MAXI J1820+070 was discovered during its 2018 outburst and was extensively monitored across the electromagnetic spectrum. Following the detection of relativistic radio jets, we obtained four Chandra X-ray observations taken between 2018 November and 2019 May, along with radio observations conducted with the VLA and MeerKAT arrays. We report the discovery of X-ray sources associated with the radio jets moving at relativistic velocities with a possible deceleration at late times. The broadband spectra of the jets are consistent with synchrotron radiation from particles accelerated up to very high energies (>10 TeV) by shocks produced by the jets interacting with the interstellar medium. The minimal internal energy estimated from the X-ray observations for the jets is $\sim 10^{41}$ erg, significantly larger than the energy calculated from the radio flare alone, suggesting most of the energy is possibly not radiated at small scales but released through late-time interactions., Accepted for publication in ApJL

Ly$\alpha$ emission is a standard tracer of starburst galaxies at high redshift. However, a number of local Ly$\alpha$ emitters (LAEs) are X-ray sources, suggesting a possible origin of Ly$\alpha$ photons other than young, hot stars, and which may be active at much later ages relative to the parent starburst. Resolved, nearby LAEs offer the opportunity to discriminate between diffuse X-ray emission arising from supernova-heated gas, high-mass X-ray binaries (HMXBs), or low-luminosity active galactic nuclei (LLAGN). We examine archival X-ray imaging from Chandra and XMM-Newton for 11 galaxies with spatially resolved Ly$\alpha$ imaging to determine the luminosity, morphology, and spectral hardness of the X-ray sources. The data are consistent with 9 of the 12, bright Ly$\alpha$ sources being driven by luminous, $10^{40}$ erg s$^{-1}$ X-ray sources. Half of the 8 Chandra sources are unresolved. The data suggest that nuclear activity, whether from LLAGN or nuclear starbursts, may play an important role in Ly$\alpha$ emission. Our results also suggest a significant link between Ly$\alpha$ emission and HMXBs, ULXs, and/or LLAGN, which would imply that Ly$\alpha$ may be generated over timescales 1 - 2 orders of magnitude longer than produced by photoionization from OB stars. This highlights a critical need to quantify the relative contributions of different sources across cosmic time, to interpret Ly$\alpha$ observations and the resulting properties of distant galaxies., Comment: 10 pages, 3 figures, 2 tables. Accepted by ApJ Letters

We report on deep Chandra X-ray Telescope imaging observations of 4C 63.20, one of the few known radio galaxies at z>3.5. The X-ray counterpart is resolved into a core plus two off-nuclear sources that (combined) account for close to 30% of the total X-ray flux. Their morphology and orientation are consistent with a diffuse, lobe-like nature, albeit compact hotspots cannot be ruled out. The broadband spectral energy distribution of 4C 63.20 can be reproduced with a jet model where the majority of the radio flux can be ascribed to synchrotron emission from the hotspots, whereas the (non-nuclear) X-ray emission is produced via Inverse Compton (IC) off of Cosmic Microwave Background (CMB) photons within the extended lobes. This scenario is broadly consistent with the expectation from highly magnetized lobes in a hotter CMB, and supports the view that IC/CMB may quench less extreme radio lobes at high redshifts., 10 pages, 8 figures, accepted to MNRAS

Black holes in binary systems execute patterns of outburst activity where two characteristic X-ray states are associated with different behaviours observed at radio wavelengths. The hard state is associated with radio emission indicative of a continuously replenished, collimated, relativistic jet, whereas the soft state is rarely associated with radio emission, and never continuously, implying the absence of a quasi-steady jet. Here we report radio observations of the black hole transient MAXI J1820+070 during its 2018 outburst. As the black hole transitioned from the hard to soft state, we observed an isolated radio flare, which, using high-angular-resolution radio observations, we connect with the launch of bipolar relativistic ejecta. This flare occurs as the radio emission of the core jet is suppressed by a factor of over 800. We monitor the evolution of the ejecta over 200 days and to a maximum separation of 10″, during which period it remains detectable due to in situ particle acceleration. Using simultaneous radio observations sensitive to different angular scales, we calculate an accurate estimate of energy content of the approaching ejection. This energy estimate is far larger than that derived from the state transition radio flare, suggesting a systematic underestimate of jet energetics. © 2020, The Author(s), under exclusive licence to Springer Nature Limited., J.S.B. acknowledges the support of a Science and Technologies Facilities Council Studentship. E.T. acknowledges financial support from the UnivEarthS Labex programme of Sorbonne Paris Cite (ANR-10-LABX-0023 and ANR-11-IDEX-0005-02). D.A.H.B. acknowledges support by the National Research Foundation. P.A.W. acknowledges support from the NRF and UCT. J.C.A.M.-J. is the recipient of an Australian Research Council Future Fellowship (FT140101082), funded by the Australian government. A.H. acknowledges that this research was supported by a grant from the GIF, the German-Israeli Foundation for Scientific Research and Development. I.H. and D.R.A.W. acknowledge support from the Oxford Hintze Centre for Astrophysical Surveys, which is funded through generous support from the Hintze Family Charitable Foundation. J.M. acknowledges financial support from the State Agency for Research of the Spanish MCIU through the 'Center of Excellence Severo Ochoa' award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709) and from the grant RTI2018-096228-B-C31 (MICIU/FEDER, EU). The MeerKAT telescope is operated by the South African Radio Astronomy Observatory, which is a facility of the National Research Foundation, an agency of the Department of Science and Technology. We thank the staff of the Mullard Radio Astronomy Observatory for their invaluable assistance in the commissioning, maintenance and operation of AMI, which is supported by the universities of Cambridge and Oxford. We acknowledge support from the European Research Council under grant ERC-2012-StG-307215 LODESTONE. We thank the Swift team for performing observations promptly on short notice. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. e-MERLIN is a National Facility operated by the University of Manchester at Jodrell Bank Observatory on behalf of STFC. We acknowledge the use of the Inter-University Institute for Data Intensive Astronomy (IDIA) data-intensive research cloud for data processing. IDIA is a South African university partnership involving the University of Cape Town, the University of Pretoria and the University of the Western Cape. We thank the International Space Science Institute in Bern, Switzerland for support and hospitality for the team meeting 'Looking at the disc-jet coupling from different angles: inclination dependence of black-hole accretion observables'.

Cette contribution porte sur un type de communication persuasive qui est de plus en plus développée aujourd’hui, à savoir la publicité sociétale. Ayant observé un corpus de 20 campagnes du point de vue de la sémantique et pragmatique énonciatives, et de l’analyse du discours et de l’argumentation, nous fournirons de nombreux exemples afin de montrer quelques caractéristiques majeures de ces messages. Une grille d’analyse sera proposée, qui s’articule autour du niveau linguistique sémantico-énonciatif, du niveau pragmatique illocutoire et du niveau rhétorique ; enfin, des remarques globales seront faites par rapport à la visée perlocutoire des campagnes.

Little is known about the properties of the accretion flows and jets of the lowest-luminosity quiescent black holes. We report new, strictly simultaneous radio and X-ray observations of the nearby stellar-mass black hole X-ray binary GS 2000+25 in its quiescent state. In deep Chandra observations we detect the system at a faint X-ray luminosity of $L_X = 1.1^{+1.0}_{-0.7} \times 10^{30}\,(d/2 {\rm \,\, kpc})^2$ erg s$^{-1}$ (1-10 keV). This is the lowest X-ray luminosity yet observed for a quiescent black hole X-ray binary, corresponding to an Eddington ratio $L_X/L_{\rm Edd} \sim 10^{-9}$. In 15 hours of observations with the Karl G. Jansky Very Large Array, no radio continuum emission is detected to a $3��$ limit of $< 2.8\ ��$Jy at 6 GHz. Including GS 2000+25, four quiescent stellar-mass black holes with $L_X < 10^{32}$ erg s$^{-1}$ have deep simultaneous radio and X-ray observations and known distances. These sources all have radio to X-ray luminosity ratios generally consistent with, but slightly lower than, the low state radio/X-ray correlation for stellar-mass black holes with $L_X > 10^{32}$ erg s$^{-1}$. Observations of these sources tax the limits of our current X-ray and radio facilities, and new routes to black hole discovery are needed to study the lowest-luminosity black holes., 7 pages, 2 figures, accepted for publication in ApJ

Aim Thoracic aortic aneurysms are a life-threatening condition often diagnosed too late. To discover novel robust biomarkers, we aimed to better understand the molecular mechanisms underlying aneurysm formation.Methods and results In Fibulin-4(R/R) mice, the extracellular matrix protein Fibulin-4 is 4-fold reduced, resulting in progressive ascending aneurysm formation and early death around 3 months of age. We performed proteomics and genomics studies on Fibulin-4(R/R) mouse aortas. Intriguingly, we observed alterations in mitochondrial protein composition in Fibulin-4(R/R) aortas. Consistently, functional studies in Fibulin-4(R/R) vascular smooth muscle cells (VSMCs) revealed lower oxygen consumption rates, but increased acidification rates. Yet, mitochondria in Fibulin-4(R/R) VSMCs showed no aberrant cytoplasmic localization. We found similar reduced mitochondrial respiration in Tgfbr-1(M318R/+) VSMCs, a mouse model for Loeys-Dietz syndrome (LDS). Interestingly, also human fibroblasts from Marfan (FBN1) and LDS (TGFBR2 and SMAD3) patients showed lower oxygen consumption. While individual mitochondrial Complexes I-V activities were unaltered in Fibulin-4(R/R) heart and muscle, these tissues showed similar decreased oxygen consumption. Furthermore, aortas of aneurysmal Fibulin-4(R/R) mice displayed increased reactive oxygen species (ROS) levels. Consistent with these findings, gene expression analyses revealed dysregulation of metabolic pathways. Accordingly, blood ketone levels of Fibulin-4(R/R) mice were reduced and liver fatty acids were decreased, while liver glycogen was increased, indicating dysregulated metabolism at the organismal level. As predicted by gene expression analysis, the activity of PGC1 alpha, a key regulator between mitochondrial function and organismal metabolism, was downregulated in Fibulin-4(R/R) VSMCs. Increased TGF beta reduced PGC1 alpha levels, indicating involvement of TGF beta signalling in PGC1 alpha regulation. Activation of PGC1 alpha restored the decreased oxygen consumption in Fibulin-4(R/R) VSMCs and improved their reduced growth potential, emphasizing the importance of this key regulator.Conclusion Our data indicate altered mitochondrial function and metabolic dysregulation, leading to increased ROS levels and altered energy production, as a novel mechanism, which may contribute to thoracic aortic aneurysm formation.

This article comes from the problematic of the body in education and aims to show some poetic languages that redefine de education of the body. A deconstructive analysis of some concepts of poetic and body are done, to place them in the level of education. Form the deconstructive reading emerge aesthetic pedagogical languages that suggest a poetic education of the body as creative practices of “oneself” from a knowledge of itself, a poetic making, a learning experience and a poetic reason arise whose need is to produce forms of educational thought properly aesthetic and to return to the sensible body. Este artículo surge de la problematización del cuerpo en la educación y tiene como finalidad mostrar algunos lenguajes poéticos que resignifican la educación del cuerpo. Se hace un análisis deconstructivo de algunos conceptos de la poética y del cuerpo para ubicarlos en el plano de la educación. De la lectura deconstructiva surgen lenguajes estético pedagógicos que hacen pensar una educación poética del cuerpo como prácticas creadoras del “sí mismo” desde un saber de sí, un hacer poético, una experiencia de aprendizaje y una razón poética cuya necesidad es producir formas de pensamiento educativos propiamente estéticos y retornar al cuerpo sensible.

Similar to learning, teaching is not exclusively a cognitive matter. Teachers’ emotions play a significant role in their teaching practice. For language teachers especially, the link between teachers’ emotions, identities and well-being has been identified as a key factor in their lives (Day & Lee, 2011) as well as in their professional development (Golombek & Doran, 2014; Kubanyiova, 2012). Although teachers’ well-being is essential in remaining engaged in the profession, little empirical work has been done to investigate how teachers cope with the affective complexities of teaching. Expectations, interest and satisfaction, as well as anxiety and frustration, are often an unspoken part of a teacher’s everyday work. This empirical exploratory study aims at investigating which emotions language teachers in higher education experience and what strategies they use to self-regulate these emotions. For this purpose, we collected and analysed data from teachers in two university language centres in Germany using a variety of instruments, including questionnaires, group discussions and researchers’ logs. The data show that both positive and negative emotions occur and are related to three main sources: the learners, the teaching-learning context and the teachers themselves. In addition, we identified a number of self-regulation strategies that are affected by various factors, such as individual sensitivity or personal attitudes. This paper will focus on the crucial role that emotions seem to play in the professional well-being of university language teachers and will link to theories of emotion and teaching practice.

The `fundamental plane of black hole accretion' (FP), a relation between the radio luminosities ($L_R$), X-ray luminosities ($L_X$), and masses ($M_{BH}$) of hard/quiescent state black hole binaries and low-luminosity active galactic nuclei, suggests some aspects of black hole accretion may be scale invariant. However, key questions still exist concerning the relationship between the inflow/outflow behaviour in the `classic' hard state and quiescence, which may impact this scaling. We show that the broadband spectra of A0620-00 and~\sgra~(the least luminous stellar mass/supermassive black holes on the FP) can be modelled simultaneously with a physically-motivated outflow-dominated model where the jet power and all distances are scaled by the black hole mass. We find we can explain the data of both A0620-00 and~\sgra~(in its non-thermal flaring state) in the context of two outflow-model scenarios: (1) a synchrotron-self-Compton dominated state in which the jet plasma reaches highly sub-equipartition conditions (for the magnetic field with respect to that of the radiating particles), and (2) a synchrotron dominated state in the fast-cooling regime in which particle acceleration occurs within the inner few gravitational radii of the black hole and plasma is close to equipartition. We show that it may be possible to further discriminate between models (1) and (2) through future monitoring of its submm/IR/X-ray emission, in particular via time lags between the variable emission in these bands., 19 pages (including appendix), 6 figures, 5 tables. Accepted for publication in MNRAS

Fibrosis is a common pathologic outcome of chronic disease resulting in the replacement of normal tissue parenchyma with a collagen-rich extracellular matrix produced by myofibroblasts. Although the progenitor cell types and cellular programs giving rise to myofibroblasts through mesenchymal transition can vary between tissues and diseases, their contribution to fibrosis initiation, maintenance, and progression is thought to be pervasive. Here we showed that the ability of transforming growth factor-β (TGFβ) to efficiently induce myofibroblast differentiation of cultured epithelial cells, endothelial cells, or quiescent fibroblasts is dependent upon the induced expression and activity of dimeric calpains, a family of non-lysosomal cysteine proteases that regulate a variety of cellular events through post-translational modification of diverse substrates. siRNA-based gene silencing demonstrated that TGFβ-induced mesenchymal transition of a murine breast epithelial cell line was dependent upon induction of expression of calpain 9 (CAPN9), an isoform previously thought to be restricted to the gastrointestinal tract. Mice lacking functional CAPN9 due to biallelic targeting of Capn9 were viable and fertile, but showed overt protection from bleomycin-induced lung fibrosis, carbon tetrachloride-induced liver fibrosis, and angiotensin II-induced cardiac fibrosis and dysfunction. A predicted loss-of-function allele of CAPN9 is common in Southeast Asia, with the frequency of homozygosity matching the prediction of Hardy-Weinberg equilibrium; together with the highly spatially-restricted pattern of CAPN9 expression under physiologic circumstances and the heartiness of the murine knockout, these data provide a strong signature for tolerance of therapeutic strategies for fibrosis aimed at CAPN9 antagonism.

Introducción: El estudio de la creatividad se realiza desde diferentes criterios, al asumirse como proceso de la personalidad y tomando como base la concepción filosófica de la actividad humana. En dicho proceso debe ser tenida en cuenta la interrelación de factores que favorece a las condiciones para el desarrollo de la creatividad, así como los vínculos entre lo cognitivo y lo afectivo. Objetivo: Analizar teóricamente los fundamentos pedagógicos y psicológicos de la creatividad y su relación con el desarrollo integral de los futuros profesionales. Métodos: Se realizó una revisión sistemática de la literatura, lo cual favoreció comprender la dependencia entre sus componentes, sus vínculos y el condicionamiento que establecen en la actividad docente. Conclusiones: La inclusión de métodos creativos aún no se ha extendido en las proporciones deseadas, lo cual limita las posibilidades de desarrollo de la creatividad en los estudiantes. En la actualidad son casi inexistentes las orientaciones metodológicas que apoyen la labor docente para desarrollar la creatividad en los alumnos, en lo cual incide la escasa utilización de métodos productivos.

In systemic sclerosis (SSc), previously healthy adults develop an inflammatory prodrome with subsequent progressive fibrosis of the skin and viscera. SSc has a weak signature for genetic contribution, and there are few pathogenic insights or targeted treatments for this condition. Here, chromatin accessibility and transcriptome profiling coupled with targeted epigenetic editing revealed constitutive activation of a previously unannotated transforming growth factor-β2 (TGFB2) enhancer maintained through epigenetic memory in SSc. The resulting autocrine TGFβ2 signaling enforced a profibrotic synthetic state in ex vivo fibroblasts from patients with SSc. Inhibition of NF-κB or BRD4 achieved sustained inhibition of TGFB2 enhancer activity, mitigated profibrotic gene expression, and reversed dermal fibrosis in patient skin explants. These findings suggest a potential epigenetic mechanism of fibrosis in SSc and inform a regulatory mechanism of TGFB2, a major profibrotic cytokine.

Vascular Ehlers-Danlos Syndrome (vEDS) is an autosomal-dominant connective tissue disorder caused by heterozygous mutations in the COL3A1 gene[1][1]. Currently, loss of structural integrity of the extracellular matrix is believed to drive the signs and symptoms of this condition, including

Este articulo surge al analizar una experiencia educativa en las Ludotekas INDER (Medellín-Colombia). El objetivo del estudio es reconocer en las Ludotekas "pistas" para enseñar la Educación Corporal en su dimensión estética. El estudio muestra la necesidad de disponer signos de lo sensible para enseñar; generar experiencias sensibles a partir del juego; re-crear el enseñar para hacer del aula un espacio "vital"; y una forma de distribución de lo sensible para orientar una clase. Con ello, se aporta a didácticas que reivindican un educar desde los cuerpos en contextos educativos formales y no-formales. This article arises from analyzing an educational experience in the INDER Play Rooms (Medellin, Colombia). The objective of the study is to recognize in the Play Rooms "tracks" to teach Body Education in its aesthetic dimension. The study shows the need for signs of the sensitive to teach; to generate sensitive experiences from the game; to re-create teaching in order to make the classroom a "vital" space; and a form of distribution of the sensitive to guide a class. In doing so, it is provided to didactics, which demand an education from the bodies in formal and non-formal educational contexts.

As an evolutionary phase of galaxies, active galactic nuclei (AGN) over a large range of redshift have been utilized for understanding cosmic evolution. In particular, the population and evolution of AGNs have been investigated through the study of the cosmic X-ray background in various fields. As one of the deep fields observed by Chandra with a total of 2.8 Msec exposures, Abell 133 is a special region to investigate AGNs, providing a testbed for probing the environmental effect on AGN trigger, since cluster environments can be different from field environments. The achieved flux limit of data at 50% completeness level of 6.95x10^(-16), 1.43x10^(-16), and 1.57x10^(-15) ergs cm^(-2) in 0.5-8, 0.5-2, and 2-8 keV. Using the wavdetect and no-source binomial probability (i.e., p, Accepted for publication in ApJ. 11 pages, 12 figures

Building on recent work by Chandar et al. (2020), we construct X-ray luminosity functions (XLFs) for different classes of X-ray binary (XRB) donors in the nearby star-forming galaxy M83 through a novel methodology: rather than classifying low- vs. high-mass XRBs based on the scaling of the number of X-ray sources with stellar mass and star formation rate, respectively, we utilize multi-band Hubble Space Telescope imaging data to classify each Chandra-detected compact X-ray source as a low-mass (i.e. donor mass ~ 8 solar masses) or intermediate-mass XRB based on either the location of its candidate counterpart on optical color-magnitude diagrams or the age of its host star cluster. In addition to the the standard (single and/or truncated) power-law functional shape, we approximate the resulting XLFs with a Schechter function. We identify a marginally significant (at the 1-to-2 sigma level) exponential downturn for the high-mass XRB XLF, at logLx ~ 38.48^{+0.52}_{-0.33} (in log CGS units). In contrast, the low- and intermediate-mass XRB XLFs, as well as the total XLF of M83, are formally consistent with sampling statistics from a single power-law. Our method suggests a non-negligible contribution from low- and possibly intermediate-mass XRBs to the total XRB XLF of M83, i.e. between 20 and 50%, in broad agreement with X-ray based XLFs. More generally, we caution against considerable contamination from X-ray emitting supernova remnants to the published, X-ray based XLFs of M83, and possibly all actively star-forming galaxies., Comment: 18 pages (text, 44 with figures), 8 figures + 1 long figure, 1 table + 1 long table. Accepted by ApJ

Thoracic aortic aneurysms (TAA) are permanent and localized dilations of the aorta that predispose patients to a life-threatening risk of aortic dissection or rupture. The identification of pathogenic variants that cause hereditary forms of TAA has delineated fundamental molecular processes required to maintain aortic homeostasis. Vascular smooth muscle cells (VSMCs) elaborate and remodel the extracellular matrix (ECM) in response to mechanical and biochemical cues from their environment. Causal variants for hereditary forms of aneurysm compromise the function of gene products involved in the transmission or interpretation of these signals, initiating processes that eventually lead to degeneration and mechanical failure of the vessel. These include mutations that interfere with transduction of stimuli from the matrix to the actin–myosin cytoskeleton through integrins, and those that impair signaling pathways activated by transforming growth factor-β (TGF-β). In this review, we summarize the features of the healthy aortic wall, the major pathways involved in the modulation of VSMC phenotypes, and the basic molecular functions impaired by TAA-associated mutations. We also discuss how the heterogeneity and balance of adaptive and maladaptive responses to the initial genetic insult might contribute to disease.

We present coordinated multiwavelength observations of the high Galactic latitude (b=+50 deg) black hole X-ray binary (XRB) J1357.2-0933 in quiescence. Our broadband spectrum includes strictly simultaneous radio and X-ray observations, and near-infrared, optical, and ultraviolet data taken 1-2 days later. We detect Swift J1357.2-0933 at all wavebands except for the radio (f_5GHz < 3.9 uJy/beam). Given current constraints on the distance (2.3-6.3 kpc), its 0.5-10 keV X-ray flux corresponds to an Eddington ratio Lx/Ledd = 4e-9 -- 3e-8 (assuming a black hole mass of 10 Msun). The broadband spectrum is dominated by synchrotron radiation from a relativistic population of outflowing thermal electrons, which we argue to be a common signature of short-period quiescent BHXBs. Furthermore, we identify the frequency where the synchrotron radiation transitions from optically thick-to-thin (approximately 2-5e14 Hz, which is the most robust determination of a 'jet break' for a quiescent BHXB to date. Our interpretation relies on the presence of steep curvature in the ultraviolet spectrum, a frequency window made observable by the low amount of interstellar absorption along the line of sight. High Galactic latitude systems like Swift J1357.2-0933 with clean ultraviolet sightlines are crucial for understanding black hole accretion at low luminosities., 12 pages, 5 Figures, 1 Table. Accepted for publication in MNRAS

We report on Chandra gratings spectra of the stellar-mass black hole GRS 1915+105 obtained during a novel, highly obscured state. As the source entered this state, a dense, massive accretion disk wind was detected through strong absorption lines. Photionization modeling indicates that it must originate close to the central engine, orders of magnitude from the outer accretion disk. Strong, nearly sinusoidal flux variability in this phase yielded a key insight: the wind is blue-shifted when its column density is relatively low, but red-shifted as it approaches the Compton-thick threshold. At no point does the wind appear to achieve the local escape velocity; in this sense, it is a "failed wind." Later observations suggest that the disk ultimately fails to keep even the central engine clear of gas, leading to heavily obscured and Compton-thick states characterized by very strong Fe K emission lines. Indeed, these later spectra are successfully described using models developed for obscured AGN. We discuss our results in terms the remarkable similarity of GRS 1915+105 deep in its "obscured state" to Seyfert-2 and Compton-thick AGN, and explore how our understanding of accretion and obscuration in massive black holes is impacted by our observations., Submitted to ApJ

The objective of the present study was to 1) analyze the ascending aortic proteome within a mouse model of Marfan syndrome (MFS; Fbn1C1041G/+) at early and late stages of aneurysm and 2) subsequently test a novel hypothesis formulated on the basis of this unbiased proteomic screen that links changes in integrin composition to transforming growth factor (TGF)-β-dependent activation of the rapamycin-independent component of mammalian target of rapamycin (Rictor) signaling pathway. Ingenuity Pathway Analysis of over 1,000 proteins quantified from the in vivo MFS mouse aorta by data-independent acquisition mass spectrometry revealed a predicted upstream regulator, Rictor, that was selectively activated in aged MFS mice. We validated this pattern of Rictor activation in vivo by Western blot analysis for phosphorylation on Thr1135 in a separate cohort of mice and showed in vitro that TGF-β activates Rictor in an integrin-linked kinase-dependent manner in cultured aortic vascular smooth muscle cells. Expression of β3-integrin was upregulated in the aged MFS aorta relative to young MFS mice and wild-type mice. We showed that β3-integrin expression and activation modulated TGF-β-induced Rictor phosphorylation in vitro, and this signaling effect was associated with an altered vascular smooth muscle cell proliferative-migratory and metabolic in vitro phenotype that parallels the in vivo aneurysm phenotype in MFS. These results reveal that Rictor is a novel, context-dependent, noncanonical TGF-β signaling effector with potential pathogenic implications in aortic aneurysm. NEW & NOTEWORTHY We present the most comprehensive quantitative analysis of the ascending aortic aneurysm proteome in Marfan syndrome to date resulting in novel and potentially wide-reaching findings that expression and signaling by β3-integrin constitute a modulator of transforming growth factor-β-induced rapamycin-independent component of mammalian target of rapamycin (Rictor) signaling and physiology in aortic vascular smooth muscle cells.

We report on a 120 ks Chandra/HETG spectrum of the black hole GRS 1915+105. The observation was made during an extended and bright soft state in June, 2015. An extremely rich disk wind absorption spectrum is detected, similar to that observed at lower sensitivity in 2007. The very high resolution of the third-order spectrum reveals four components to the disk wind in the Fe K band alone; the fastest has a blue-shift of v = 0.03c. Broadened re-emission from the wind is also detected in the first-order spectrum, giving rise to clear accretion disk P Cygni profiles. Dynamical modeling of the re-emission spectrum gives wind launching radii of r ~ 10^(2-4) GM/c^2. Wind density values of n ~ 10^(13-16) cm^-3 are then required by the ionization parameter formalism. The small launching radii, high density values, and inferred high mass outflow rates signal a role for magnetic driving. With simple, reasonable assumptions, the wind properties constrain the magnitude of the emergent magnetic field to B ~ 10^(3-4) Gauss if the wind is driven via magnetohydrodynamic (MHD) pressure from within the disk, and B ~ 10^(4-5) Gauss if the wind is driven by magnetocentrifugal acceleration. The MHD estimates are below upper limits predicted by the canonical alpha-disk model (Shakura & Sunyaev 1973). We discuss these results in terms of fundamental disk physics and black hole accretion modes., Accepted for publication in ApJ Letters

Women with Marfan syndrome (MFS) are at high risk for pregnancy-associated aortic dissection. Pathogenic models that singularly invoke hemodynamic stress are difficult to reconcile with predominant postnatal occurrence of aortic tear, often occurring weeks to months after delivery. In consideration of events that peak at term, are sustained after delivery, and might synergize with previously defined signaling pathways implicated in aneurysm progression, we examined the hormone oxytocin, which initiates uterine contraction and milk letdown for the duration of lactation through phosphorylation of extracellular signal-regulated kinase (ERK). In a mouse model of MFS that shows highly penetrant postnatal aortic dissection, risk was strongly attenuated by preventing lactation or use of an oxytocin receptor antagonist. Survival correlated inversely with the extent of ERK activation in the aortic wall, and strong protection was observed upon attenuation of ERK phosphorylation using an inhibitor of ERK kinase (MEK) or the U.S. Food and Drug Administration-approved medication hydralazine, offering potential therapeutic strategies for pregnancy-associated vascular catastrophe in the setting of MFS.

Alberti La Marmora Francesco, Gallo Elena. Il patrimonio materiale e immateriale di una famiglia aristocratica: gli archivi Alberti La Marmora. In: La Gazette des archives, n°249, 2018-1. Les archivistes au centre du patrimoine culturel. Actes du VIIIe colloque des archivistes de l’Arc alpin occidental 12-14 octobre 2017. pp. 149-161.

RESUMEN: Este artículo surge de la problematización del cuerpo en la educación y tiene como finalidad mostrar algunos lenguajes poéticos que resignifican la educación del cuerpo. Se hace un análisis deconstructivo de algunos conceptos de la poética y del cuerpo para ubicarlos en el plano de la educación. De la lectura deconstructiva surgen lenguajes estético pedagógicos que hacen pensar una educación poética del cuerpo como prácticas creadoras del “sí mismo” desde un saber de sí, un hacer poético, una experiencia de aprendizaje y una razón poética cuya necesidad es producir formas de pensamiento educativos propiamente estéticos y retornar al cuerpo sensible. ABSTRACT: This article comes from the problematic of the body in education and aims to show some poetic languages that redefine de education of the body. A deconstructive analysis of some concepts of poetic and body are done, to place them in the level of education. Form the deconstructive reading emerge aesthetic pedagogical languages that suggest a poetic education of the body as creative practices of “oneself” from a knowledge of itself, a poetic making, a learning experience and a poetic reason arise whose need is to produce forms of educational thought properly aesthetic and to return to the sensible body. COL0043093

We conduct a detailed case-study of the interstellar shell near the high-mass X-ray binary, Cygnus X-1. We present new WIYN optical spectroscopic and Chandra X-ray observations of this region, which we compare with detailed MAPPINGS III shock models, to investigate the outflow powering the shell. Our analysis places improved, physically motivated constraints on the nature of the shockwave and the interstellar medium (ISM) it is plowing through. We find that the shock is traveling at less than a few hundred km/s through a low-density ISM (< 5 cm^-3). We calculate a robust, 3 sigma upper limit to the total, time-averaged power needed to drive the shockwave and inflate the bubble, < 2 x 10^38 erg/s. We then review possible origins of the shockwave. We find that a supernova origin to the shockwave is unlikely and that the black hole jet and/or O-star wind can both be central drivers of the shockwave. We conclude that the source of the Cygnus X-1 shockwave is far from solved., 16 pages, 8 figures, accepted for publication in MNRAS

Pemphigus foliaceus is a blistering autoimmune disease related to the production of autoantibodies against desmoglein 1. We present a patient with psoriasis and pemphigus foliaceus aggravated by enalapril and amlodipine intake, with successful response of both conditions to adalimumab therapy.El pénfigo foliáceo es una enfermedad autoinmune ampollosa debida a la producción de autoanticuerpos frente a la desmogleína 1. Presentamos el caso de un paciente con psoriasis y pénfigo foliáceo agravado por enalapril y amlodipino, con buena respuesta de ambas patologías a la terapia con adalimumab.Pemphigus foliaceus is a blistering autoimmune disease related to the production of autoantibodies against desmoglein 1. We present a patient with psoriasis and pemphigus foliaceus aggravated by enalapril and amlodipine intake, with successful response of both conditions to adalimumab therapy.El pénfigo foliáceo es una enfermedad autoinmune ampollosa debida a la producción de autoanticuerpos frente a la desmogleína 1. Presentamos el caso de un paciente con psoriasis y pénfigo foliáceo agravado por enalapril y amlodipino, con buena respuesta de ambas patologías a la terapia con adalimumab.

The transforming growth factor β (TGF-β) family of signaling molecules, which includes TGF-βs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-β family members play different roles in these tissues, and their activities are often balanced with those of other TGF-β family members and by interactions with other signaling pathways. Perturbations in TGF-β family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-β family of signaling mediators and the extracellular matrix in connective tissues.

RGG 118 (SDSS 1523+1145) is a nearby ($z=0.0243$), dwarf disk galaxy ($M_{\ast}\approx2\times10^{9} M_{\odot}$) found to host an active $\sim50,000$ solar mass black hole at its core (Baldassare et al. 2015). RGG 118 is one of a growing collective sample of dwarf galaxies known to contain active galactic nuclei -- a group which, until recently, contained only a handful of objects. Here, we report on new \textit{Hubble Space Telescope} Wide Field Camera 3 UVIS and IR imaging of RGG 118, with the main goal of analyzing its structure. Using 2-D parametric modeling, we find that the morphology of RGG 118 is best described by an outer spiral disk, inner component consistent with a pseudobulge, and central PSF. The luminosity of the PSF is consistent with the central point source being dominated by the AGN. We measure the luminosity and mass of the "pseudobulge" and confirm that the central black hole in RGG 118 is under-massive with respect to the $M_{BH}-M_{\rm bulge}$ and $M_{BH}-L_{\rm bulge}$ relations. This result is consistent with a picture in which black holes in disk-dominated galaxies grow primarily through secular processes., Accepted to Astrophysical Journal. 11 pages, 8 figures

Background Epstein-Barr virus (EBV) has been associated with inflammation in the colon, particularly in patients with inflammatory bowel disease (IBD). Even if a relevant plasmocytosis, similar to IBD, is present in microscopic colitis (MC), the frequency of EBV infection in this setting is unknown. Objectives We aimed to compare the frequency of colonic EBV infection in patients with MC, ulcerative colitis (UC), and irritable bowel syndrome (IBS). Study design The frequency of colonic EBV infection in biopsies of 30 patients with MC, 30 patients with UC, and 30 controls with IBS was retrospectively assessed. PCR was performed to detect viral EBV DNA in colonic biopsies. In situ hybridization was also performed to identify and localize EBV-encoded small RNA1 and 2 (EBERs) within cells. Results The presence of EBV DNA was detected in 27 out of 30 MC patients, in 20 out of 30 UC cases, and in none of IBS group. The frequency of EBV DNA in MC was significantly higher compared with that reported in UC (90.0% vs. 66.7%, p = 0.03). EBERs+ cells were observed in 18 out of 30 MC patients, in only 3 out of 30 UC patients (60.0% vs. 10.0%, p Conclusions EBV infection is almost always detectable in the colonic mucosa of patients with MC. Further studies are necessary to confirm this association and to clarify the role of EBV in MC and, more generally, in colonic inflammation.

Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction and shared biochemical and cellular mechanisms underlying ectopic calcification in PXE and related disorders caused by defined perturbations in extracellular adenosine 5′-triphosphate catabolism. Under osteogenic culture conditions, ABCC6 mutant cells calcified, suggesting a provoked cell-autonomous defect. Using a conditional Abcc6 knockout mouse model, we excluded the prevailing pathogenic hypothesis that singularly invokes failure of hepatic secretion of an endocrine inhibitor of calcification. Instead, deficiency of Abcc6 in both local and distant cells was necessary to achieve the early onset and penetrant ectopic calcification observed upon constitutive gene targeting. ABCC6 mutant cells additionally had increased expression and activity of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme that degrades pyrophosphate, a major inhibitor of calcification. A selective and orally bioavailable TNAP inhibitor prevented calcification in ABCC6 mutant cells in vitro and attenuated both the development and progression of calcification in Abcc6 −/− mice in vivo, without the deleterious effects on bone associated with other proposed treatment strategies.

Background/aim An association has been reported between lung cancer and John Cunningham (JC) virus infection. The aim of this study was to evaluate the prevalence of JC virus in a small cohort of patients with lung adenocarcinoma and assess its presence in nodal metastasis. Materials and methods Consecutive samples of 13 surgically-removed lung tumors and 13 surrounding normal cancer-free tissues were selected. Five cases included metastatic lymph nodes. JC virus infection was assessed through nested PCR. Results Seven out of thirteen patients with lung adenocarcinoma had a positive PCR test for JC virus. One of the five patients with nodal metastasis had a positive PCR test for JC virus. None of the thirteen specimens from the control group presented with JC virus infection. The difference between the two groups regarding JC virus infection was statistically significant (p=0.008). Conclusion Our study suggests that JC virus might be involved in lung carcinogenesis.

In an effort to understand the cause of the apparent depletion in the number density of radio-loud AGNs at $z>3$, this work investigates the viability of the so-called Cosmic Microwave Background (CMB) quenching mechanism of intrinsically jetted, high-z AGNs, whereby Inverse Compton scattering of CMB photons off electrons within the extended lobes results in a substantial dimming of the lobe synchrotron emission at GHz frequencies, while simultaneously boosting their diffuse X-ray signal. We focus on five $z>3.5$ radio galaxies that have sufficiently deep Chandra exposure (> 50 ks) to warrant a meaningful investigation of any extended X-ray emission. For those objects with evidence for statistically significant extended X-ray lobes (4C 41.17 and 4C 03.24), we combine the Chandra measurements with literature data at lower frequencies to assemble the systems' Spectral Energy Distributions (SEDs), and utilize state-of-the-art SED modelling (Ghisellini et al. 2015) -- including emission from the disk, torus, jet, hotspots, and lobes -- to infer their physical parameters. For both radio galaxies, the magnetic energy density in the hotspots is found to exceed the energy density in CMB photons, wheres the opposite is true for the lobes. This implies that any extended synchrotron emission likely originates from the hotspots themselves, rather than the lobes. Conversely, Inverse Compton scattering of CMB photons dominates the extended X-ray emission from the lobes, which are effectively "radio-quenched". As a result, CMB quenching is effective in these systems in spite of the fact that the observed X-ray to radio luminosity ratio does not bear the signature $(1+z)^4$ dependence of the CMB energy density., MNRAS in press; 17 pages, 8 figures, 4 tables

We present simultaneous X-ray and radio observations of the black hole X-ray binary V404 Cygni at the end of its 2015 outburst. From 2015 July 11-August 5 we monitored V404 Cygni with Chandra, Swift, and NuSTAR in the X-ray, and with the Karl G. Jansky Very Large Array and the Very Long Baseline Array in the radio, spanning a range of luminosities that were poorly covered during its previous outburst in 1989 (our 2015 campaign covers 2e33, Comment: 24 pages, 11 figures, 5 tables. Accepted for publication in ApJ