The Human Metapneumovirus Matrix Protein Stimulates the Inflammatory Immune Response In Vitro

Each year, during winter months, human Metapneumovirus (hMPV) is associated with epidemics of bronchiolitis resulting in the hospitalization of many infants. Bronchiolitis is an acute illness of the lower respiratory tract with a consequent inflammation of the bronchioles. The rapid onset of inflammation suggests the innate immune response may have a role to play in the pathogenesis of this hMPV infection. Since, the matrix protein is one of the most abundant proteins in the Paramyxoviridae family virion, we hypothesized that the inflammatory modulation observed in hMPV infected patients may be partly associated with the matrix protein (M-hMPV) response. By western blot analysis, we detected a soluble form of M-hMPV released from hMPV infected cell as well as from M-hMPV transfected HEK 293T cells suggesting that M-hMPV may be directly in contact with antigen presenting cells (APCs) during the course of infection. Moreover, flow cytometry and confocal microscopy allowed determining that M-hMPV was taken up by dendritic cells (moDCs) and macrophages inducing their activation. Furthermore, these moDCs enter into a maturation process inducing the secretion of a broad range of inflammatory cytokines when exposed to M-hMPV. Additionally, M-hMPV activated DCs were shown to stimulate IL-2 and IFN-γ production by allogeneic T lymphocytes. This M-hMPV-mediated activation and antigen presentation of APCs may in part explain the marked inflammatory immune response observed in pathology induced by hMPV in patients

The Mid-Infrared Environments of High-Redshift Radio Galaxies

Taking advantage of the impressive sensitivity of Spitzer to detect massive galaxies at high redshift, we study the mid-infrared environments of powerful, high-redshift radio galaxies at 1.2<z<3. Galaxy cluster member candidates were isolated using a single Spitzer/IRAC mid-infrared color criterion, [3.6]-[4.5]>-0.1 (AB), in the fields of 48 radio galaxies at 1.2<z<3. This simple IRAC color selection is effective at identifying galaxies at z>1.2. Using a counts-in-cell analysis, we identify a field as overdense when 15 or more red IRAC sources are found within 1arcmin (i.e.,~0.5Mpc at 1.2<z<3) of the radio galaxy to the 5sigma flux density limits of our IRAC data (f3.6=11.0uJy, f4.5=13.4uJy). We find that radio galaxies lie preferentially in medium to dense regions, with 73% of the targeted fields denser than average. Our (shallow) 120s data permit the rediscovery of previously known clusters and protoclusters associated with radio galaxies as well as the discovery of new promising galaxy cluster candidates at z>1.2.Comment: 14 pages, 7 figures, 3 tables, accepted for publication in Ap

Histone methylation by SETD1A protects nascent DNA through the nucleosome chaperone activity of FANCD2

Components of the Fanconi anemia and homologous recombination pathways play a vital role in protecting newly replicated DNA from uncontrolled nucleolytic degradation, safeguarding genome stability. Here we report that histone methylation by the lysine methyltransferase SETD1A is crucial for protecting stalled replication forks from deleterious resection. Depletion of SETD1A sensitizes cells to replication stress and leads to uncontrolled DNA2-dependent resection of damaged replication forks. The ability of SETD1A to prevent degradation of these structures is mediated by its ability to catalyze methylation on Lys4 of histone H3 (H3K4) at replication forks, which enhances FANCD2-dependent histone chaperone activity. Suppressing H3K4 methylation or expression of a chaperone-defective FANCD2 mutant leads to loss of RAD51 nucleofilament stability and severe nucleolytic degradation of replication forks. Our work identifies epigenetic modification and histone mobility as critical regulatory mechanisms in maintaining genome stability by restraining nucleases from irreparably damaging stalled replication forks

The Spitzer High Redshift Radio Galaxy Survey

We present results from a comprehensive imaging survey of 70 radio galaxies at redshifts 1<z<5.2 using all three cameras onboard the Spitzer Space Telescope. The resulting spectral energy distributions unambiguously show a stellar population in 46 sources and hot dust emission associated with the active nucleus in 59. Using a new restframe S_3um/S_1.6um versus S_um/S_3um criterion, we identify 42 sources where the restframe 1.6um emission from the stellar population can be measured. For these radio galaxies, the median stellar mass is high, 2x10^11 M_sun, and remarkably constant within the range 13, there is tentative evidence for a factor of two decrease in stellar mass. This suggests that radio galaxies have assembled the bulk of their stellar mass by z~3, but confirmation by more detailed decomposition of stellar and AGN emission is needed. The restframe 500 MHz radio luminosities are only marginally correlated with stellar mass but are strongly correlated with the restframe 5um hot dust luminosity. This suggests that the radio galaxies have a large range of Eddington ratios. We also present new Very Large Array 4.86 and 8.46 GHz imaging of 14 radio galaxies and find that radio core dominance --- an indicator of jet orientation --- is strongly correlated with hot dust luminosity. While all of our targets were selected as narrow-lined, type 2 AGNs, this result can be understood in the context of orientation-dependent models if there is a continuous distribution of orientations from obscured type 2 to unobscured type 1 AGNs rather than a clear dichotomy. Finally, four radio galaxies have nearby (<6") companions whose mid-IR colors are suggestive of their being AGNs. This may indicate an association between radio galaxy activity and major mergers.Comment: 31 pages, 125 figures. Accepted for publication in the Astrophysical Journa

The mysterious morphology of MRC0943-242 as revealed by ALMA and MUSE

© 2016 ESO. We present a pilot study of the z = 2.923 radio galaxy MRC0943-242, where we combine information from ALMA and MUSE data cubes for the first time. Even with modest integration times, we disentangle the AGN and starburst dominated components. These data reveal a highly complex morphology as the AGN, starburst, and molecular gas components show up as widely separated sources in dust continuum, optical continuum, and CO line emission observations. CO(1-0) and CO(8-7) line emission suggest that there is a molecular gas reservoir offset from both the dust and the optical continuum that is located ~90 kpc from the AGN. The UV line emission has a complex structure in emission and absorption. The line emission is mostly due to a large scale ionisation cone energised by the AGN, and a Lya emitting bridge of gas between the radio galaxy and a heavily star-forming set of components. Strangely, the ionisation cone has no Lya emission. We find this is due to an optically thick layer of neutral gas with unity covering fraction spread out over a region of at least ~100 kpc from the AGN. Other less thick absorption components are associated with Lya emitting gas within a few tens of kpc from the radio galaxy and are connected by a bridge of emission. We speculate that this linear structure of dust, Lya and CO emission, and the redshifted absorption seen in the circum nuclear region may represent an accretion flow feeding gas into this massive AGN host galaxy

The galaxy cluster mid-infrared luminosity function at 1.3 < z <3.2

We present 4.5 μm luminosity functions for galaxies identified in 178 candidate galaxy clusters at 1.3 1.3. The luminosity functions are derived for different redshift and richness bins, and the IRAC imaging reaches depths of m∗ + 2, allowing us to measure the faint end slopes of the luminosity functions. We find that α = −1 describes the luminosity function very well in all redshift bins and does not evolve significantly. This provides evidence that the rate at which the low mass galaxy population grows through star formation gets quenched and is replenished by in-falling field galaxies does not have a major net effect on the shape of the luminosity function. Our measurements for m∗ are consistent with passive evolution models and high formation redshifts (zf ∼ 3). We find a slight trend toward fainter m∗ for the richest clusters, implying that the most massive clusters in our sample could contain older stellar populations, yet another example of cosmic downsizing. Modeling shows that a contribution of a star-forming population of up to 40% cannot be ruled out. This value, found from our targeted survey, is significantly lower than the values found for slightly lower redshift, z ∼ 1, clusters found in wide-field surveys. The results are consistent with cosmic downsizing, as the clusters studied here were all found in the vicinity of RLAGNs—which have proven to be preferentially located in massive dark matter halos in the richest environments at high redshift—and they may therefore be older and more evolved systems than the general protocluster population

HST grism confirmation of two z ~ 2 structures from the clusters around radio-loud AGN (CARLA) survey

Using Hubble Space Telescope slitless grism data, we report the spectroscopic confirmation of two distant structures at z ~ 2 associated with powerful high-redshift radio-loud active galactic nuclei (AGNs). These rich structures, likely (forming) clusters, are among the most distant structures currently known, and were identified on the basis of Spitzer/IRAC [3.6]–[4.5] color. We spectroscopically confirm nine members in the field of MRC 2036−254, comprising eight star-forming galaxies and the targeted radio galaxy. The median redshift is z=2.000. We spectroscopically confirm 10 members in the field of B3 0756+406, comprising 8 star-forming galaxies and 2 AGNs, including the targeted radio-loud quasar. The median redshift is z=1.986. All confirmed members are within 500 kpc (1 arcmin) of the targeted AGNs. We derive median (mean) star-formation rates of ~35 Mʘ yr‾¹ (~50 M yr‾¹) for the confirmed star-forming members of both structures based on their [O III]ʎ5007 luminosities, and estimate average galaxy stellar masses ≲1 x 10¹¹ Mʘ based on mid-infrared fluxes and spectral energy distribution modeling. Most of our confirmed members are located above the star-forming main sequence toward starburst galaxies, consistent with clusters at these early epochs being the sites of significant levels of star formation. The structure around MRC 2036−254 shows an overdensity of IRAC-selected candidate galaxy cluster members consistent with being quiescent galaxies, while the structure around B3 0756+406 shows field values, albeit with many lower limits to colors that could allow an overdensity of faint red quiescent galaxies. The structure around MRC 2036−254 shows a red sequence of passive galaxy candidates

Galaxy Clusters around Radio-loud Active Galactic Nuclei at 1.3 < z < 3.2 as Seen by Spitzer

We report the first results from the Clusters Around Radio-Loud AGN program, a Cycle 7 and 8 Spitzer Space Telescope snapshot program to investigate the environments of a large sample of obscured and unobscured luminous radio-loud active galactic nuclei (AGNs) at 1.2 –0.1 (AB), which efficiently selects high-redshift (z > 1.3) galaxies of all types, we identify galaxy cluster member candidates in the fields of the radio-loud AGN. The local density of these Infrared Array Camera (IRAC)-selected sources is compared to the density of similarly selected sources in blank fields. We find that 92% of the radio-loud AGN reside in environments richer than average. The majority (55%) of the radio-loud AGN fields are found to be overdense at a ≥2σ level; 10% are overdense at a ≥5σ level. A clear rise in surface density of IRAC-selected sources toward the position of the radio-loud AGN strongly supports an association of the majority of the IRAC-selected sources with the radio-loud AGN. Our results provide solid statistical evidence that radio-loud AGN are likely beacons for finding high-redshift galaxy (proto-)clusters. We investigate how environment depends on AGN type (unobscured radio-loud quasars versus obscured radio galaxies), radio luminosity and redshift, finding no correlation with either AGN type or radio luminosity. We find a decrease in density with redshift, consistent with galaxy evolution for this uniform, flux-limited survey. These results are consistent with expectations from the orientation-driven AGN unification model, at least for the high radio luminosity regimes considered in this sample

A large-scale galaxy structure at z = 2.02 associated with the radio galaxy MRC 0156-252

We present the spectroscopic confirmation of a structure of galaxies surrounding the radio galaxy MRC 0156-252 at z = 2.02. The structure was initially discovered as an overdensity of both near-infrared selected z > 1.6 and mid-infrared selected z > 1.2 galaxy candidates. We used the VLT/FORS2 multi-object spectrograph to target ~80 high-redshift galaxy candidates, and obtain robust spectroscopic redshifts for more than half the targets. The majority of the confirmed sources are star-forming galaxies at z > 1.5. In addition to the radio galaxy, two of its close-by companions (<6″) also show AGN signatures. Ten sources, including the radio galaxy, lie within | z − 2.020 | <0.015 (i.e., velocity offsets <1500 km s^-1) and within projected 2 Mpc comoving of the radio galaxy. Additional evidence suggests not only that the galaxy structure associated with MRC 0156-252 is a forming galaxy cluster but also that this structure is most probably embedded in a larger-scale structure

HST Grism Confirmation of 16 Structures at 1.4<z<2.8 from the Clusters Around Radio-Loud AGN (CARLA) Survey

We report spectroscopic results from our 40-orbit Hubble Space Telescope slitless grism spectroscopy program observing the 20 densest CARLA candidate galaxy clusters at 1.41.4