Clostridium difficile Toxin B causes epithelial cell necrosis through an autoprocessing-independent mechanism

Clostridium difficile is the most common cause of antibiotic-associated nosocomial infection in the United States. C. difficile secretes two homologous toxins, TcdA and TcdB, which are responsible for the symptoms of C. difficile associated disease. The mechanism of toxin action includes an autoprocessing event where a cysteine protease domain (CPD) releases a glucosyltransferase domain (GTD) into the cytosol. The GTD acts to modify and inactivate Rho-family GTPases. The presumed importance of autoprocessing in toxicity, and the apparent specificity of the CPD active site make it, potentially, an attractive target for small molecule drug discovery. In the course of exploring this potential, we have discovered that both wild-type TcdB and TcdB mutants with impaired autoprocessing or glucosyltransferase activities are able to induce rapid, necrotic cell death in HeLa and Caco-2 epithelial cell lines. The concentrations required to induce this phenotype correlate with pathology in a porcine colonic explant model of epithelial damage. We conclude that autoprocessing and GTD release is not required for epithelial cell necrosis and that targeting the autoprocessing activity of TcdB for the development of novel therapeutics will not prevent the colonic tissue damage that occurs in C. difficile - associated disease

The 1-1000 micron SEDs of far-infrared galaxies

Galaxies selected at 170um by the ISO FIRBACK survey represent the brightest \~10% of the Cosmic Infrared Background. Examining their nature in detail is therefore crucial for constraining models of galaxy evolution. Here we combine Spitzer archival data with previous near-IR, far-IR, and sub-mm observations of a representative sample of 22 FIRBACK galaxies spanning three orders of magnitude in infrared luminosity. We fit a flexible, multi-component, empirical SED model of star-forming galaxies designed to model the entire ~1-1000um wavelength range. The fits are performed with a Markov Chain Monte Carlo (MCMC) approach, allowing for meaningful uncertainties to be derived. This approach also highlights degeneracies such as between Td and beta, which we discuss in detail. From these fits and standard relations we derive: L_IR, L_PAH, SFR, tau_V, M_star, M_dust, Td, and beta. We look at a variety of correlations between these and combinations thereof in order to examine the physical nature of these galaxies. Our conclusions are supplemented by morphological examination of the sources, and comparison with local samples. We find the bulk of our sample to be consistent with fairly standard size and mass disk galaxies with somewhat enhanced star-formation relative to local spirals, but likely not bona fide starbursts. A few higher-z LIGs and ULIGs are also present, but contrary to expectation, they are weak mid-IR emitters and overall are consistent with star-formation over an extended cold region rather than concentrated in the nuclear regions. We discuss the implications of this study for understanding populations detected at other wavelengths, such as the bright 850um SCUBA sources or the faint Spitzer 24um sources.Comment: 19 pages, 20 figures, accepted for publication in MNRA

The XMM-SERVS Survey: XMM-Newton Point-source Catalogs for the W-CDF-S and ELAIS-S1 Fields

We present the X-ray point-source catalogs in two of the XMM-Spitzer Extragalactic Representative Volume Survey (XMM-SERVS) fields, W-CDF-S (4.6 deg2) and ELAIS-S1 (3.2 deg2), aiming to fill the gap between deep pencil-beam X-ray surveys and shallow X-ray surveys over large areas. The W-CDF-S and ELAIS-S1 regions were targeted with 2.3 and 1.0 Ms of XMM-Newton observations, respectively; 1.8 and 0.9 Ms exposures remain after flare filtering. The survey in W-CDF-S has a flux limit of 1.0 × 10−14 erg cm−2 s−1 over 90% of its area in the 0.5–10 keV band; 4053 sources are detected in total. The survey in ELAIS-S1 has a flux limit of 1.3 × 10−14 erg cm−2 s−1 over 90% of its area in the 0.5–10 keV band; 2630 sources are detected in total. Reliable optical-to-IR multiwavelength counterpart candidates are identified for ≈89% of the sources in W-CDF-S and ≈87% of the sources in ELAIS-S1. A total of 3129 sources in W-CDF-S and 1957 sources in ELAIS-S1 are classified as active galactic nuclei (AGNs). We also provide photometric redshifts for X-ray sources; ≈84% of the 3319/2001 sources in W-CDF-S/ELAIS-S1 with optical-to-near-IR forced photometry available have either spectroscopic redshifts or high-quality photometric redshifts. The completion of the XMM-Newton observations in the W-CDF-S and ELAIS-S1 fields marks the end of the XMM-SERVS survey data gathering. The ≈12,000 pointlike X-ray sources detected in the whole ≈13 deg2 XMM-SERVS survey will benefit future large-sample AGN studies

The star formation history of BCGs to z = 1.8 from the SpARCS/SWIRE survey : evidence for significant in situ star formation at high redshift

We present the results of an MIPS-24 μm study of the brightest cluster galaxies (BCGs) of 535 high-redshift galaxy clusters. The clusters are drawn from the Spitzer Adaptation of the Red-Sequence Cluster Survey, which effectively provides a sample selected on total stellar mass, over 0.2 12) increases rapidly with redshift. Above z ∼ 1, an average of ∼20% of the sample have 24 μm inferred infrared luminosities of LIR > 1012 Lo, while the fraction below z ∼ 1 exhibiting such luminosities is <1%. The Spitzer-IRAC colors indicate the bulk of the 24 μm detected population is predominantly powered by star formation, with only 7/125 galaxies lying within the color region inhabited by active galactic nuclei (AGNs). Simple arguments limit the star formation activity to several hundred million years and this may therefore be indicative of the timescale for AGN feedback to halt the star formation. Below redshift z ∼ 1, there is not enough star formation to significantly contribute to the overall stellar mass of the BCG population, and therefore BCG growth is likely dominated by dry mergers. Above z ∼ 1, however, the inferred star formation would double the stellar mass of the BCGs and is comparable to the mass assembly predicted by simulations through dry mergers. We cannot yet constrain the process driving the star formation for the overall sample, though a single object studied in detail is consistent with a gas-rich merger.Peer reviewe

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Extraction and Inhibition of Enzymatic Activity of Botulinum Neurotoxins/A1, /A2, and /A3 by a Panel of Monoclonal Anti-BoNT/A Antibodies

Botulinum neurotoxins (BoNTs) are extremely potent toxins that are capable of causing death or respiratory failure leading to long-term intensive care. Treatment includes serotype-specific antitoxins, which must be administered early in the course of the intoxication. Rapidly determining human exposure to BoNT is an important public health goal. In previous work, our laboratory focused on developing Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT/A–G serotypes in buffer and BoNT/A, /B, /E, and /F in clinical samples. We have previously reported the effectiveness of antibody-capture to purify and concentrate BoNTs from complex matrices, such as clinical samples. Because some antibodies inhibit or neutralize the activity of BoNT, the choice of antibody with which to extract the toxin is critical. In this work, we evaluated a panel of 16 anti-BoNT/A monoclonal antibodies (mAbs) for their ability to inhibit the in vitro activity of BoNT/A1, /A2, and /A3 complex as well as the recombinant LC of A1. We also evaluated the same antibody panel for the ability to extract BoNT/A1, /A2, and /A3. Among the mAbs, there were significant differences in extraction efficiency, ability to extract BoNT/A subtypes, and inhibitory effect on BoNT catalytic activity. The mAbs binding the C-terminal portion of the BoNT/A heavy chain had optimal properties for use in the Endopep-MS assay

The Australia Telescope Large Area Survey: Spectroscopic catalogue and radio luminosity functions

The Australia Telescope Large Area Survey (ATLAS) has surveyed 7 square degrees of sky around the Chandra Deep Field South and the European Large Area ISO Survey-South 1 fields at 1.4 GHz. ATLAS aims to reach a uniform sensitivity of 10 μJy beam−1 rms over the entire region with first data release currently reaching ∼ 30 μJy beam−1 rms. Here we present 466 new spectroscopic redshifts for radio sources in ATLAS as part of our optical follow-up programme. Of the 466 radio sources with new spectroscopic redshifts, 142 have star-forming optical spectra, 282 show evidence for active galactic nuclei (AGN) in their optical spectra, 10 have stellar spectra and 32 have spectra revealing redshifts, but with insufficient features to classify. We compare our spectroscopic classifications with two mid-infrared diagnostics and find them to be in broad agreement. We also construct the radio luminosity function for star-forming galaxies to z = 0.5 and for AGN to z = 0.8. The radio luminosity function for star-forming galaxies appears to be in good agreement with previous studies. The radio luminosity function for AGN appears higher than previous studies of the local AGN radio luminosity function. We explore the possibility of evolution, cosmic variance and classification techniques affecting the AGN radio luminosity function. ATLAS is a pathfinder for the forthcoming Evolution Map of the Universe (EMU) survey and the data presented in this paper will be used to guide EMU's survey design and early science papers

Increasing the Discovery Space in Astrophysics - A Collation of Six Submitted White Papers

We write in response to the call from the 2020 Decadal Survey to submit white papers illustrating the most pressing scientific questions in astrophysics for the coming decade. We propose exploration as the central question for the Decadal Committee's discussions.The history of astronomy shows that paradigm changing discoveries are not driven by well formulated scientific questions, based on the knowledge of the time. They were instead the result of the increase in discovery space fostered by new telescopes and instruments. An additional tool for increasing the discovery space is provided by the analysis and mining of the increasingly larger amount of archival data available to astronomers. Revolutionary observing facilities, and the state of the art astronomy archives needed to support these facilities, will open up the universe to new discovery. Here we focus on exploration for compact objects and multi messenger science. This white paper includes science examples of the power of the discovery approach, encompassing all the areas of astrophysics covered by the 2020 Decadal Survey