C9orf72-mediated ALS and FTD: multiple pathways to disease

The discovery that repeat expansions in the C9orf72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has revolutionized our understanding of these diseases. Substantial headway has been made in characterizing C9orf72-mediated disease and unravelling its underlying aetiopathogenesis. Three main disease mechanisms have been proposed: loss of function of the C9orf72 protein and toxic gain of function from C9orf72 repeat RNA or from dipeptide repeat proteins produced by repeat-associated non-ATG translation. Several downstream processes across a range of cellular functions have also been implicated. In this article, we review the pathological and mechanistic features of C9orf72-associated FTD and ALS (collectively termed C9FTD/ALS), the model systems used to study these conditions, and the probable initiators of downstream disease mechanisms. We suggest that a combination of upstream mechanisms involving both loss and gain of function and downstream cellular pathways involving both cell-autonomous and non-cell-autonomous effects contributes to disease progression

Inverse Compton X-ray halos around high-z radio galaxies: A feedback mechanism powered by far-infrared starbursts or the CMB?

We report the detection of extended X-ray emission around two powerful high-z radio galaxies (HzRGs) at z~3.6 (4C03.24 and 4C19.71) and use these to investigate the origin of extended, Inverse Compton (IC) powered X-ray halos at high z. The halos have X-ray luminosities of Lx~3e44 erg/s and sizes of ~60kpc. Their morphologies are broadly similar to the ~60-kpc long radio lobes around these galaxies suggesting they are formed from IC scattering by relativistic electrons in the radio lobes, of either CMB or FIR photons from the dust-obscured starbursts in these galaxies. These observations double the number of z>3 HzRGs with X-ray detected IC halos. We compare the IC X-ray to radio luminosity ratios for these new detections to the two previously detected z~3.8 HzRGs. Given the similar redshifts, we would expect comparable X-ray IC luminosities if CMB mm photons are the seed field for the IC emission. Instead the two z~3.6 HzRGs, which are ~4x fainter in the FIR, also have ~4x fainter X-ray IC emission. Including a further six z>2 radio sources with IC X-ray halos from the literature, we suggest that in the more compact (lobe sizes <100-200kpc), majority of radio sources, the bulk of the IC emission may be driven by scattering of locally produced FIR photons from luminous, dust-obscured starbursts within these galaxies, rather than CMB photons. The resulting X-ray emission can ionise the gas on ~100-200-kpc scales around these systems and thus form their extended Ly-alpha emission line halos. The starburst and AGN activity in these galaxies are thus combining to produce an effective and wide-spread "feedback" process, acting on the long-term gas reservoir for the galaxy. If episodic radio activity and co-eval starbursts are common in massive, high-z galaxies, then this IC-feedback mechanism may affect the star-formation histories of massive galaxies. [Abridged

Energy feedback from x-ray binaries in the early universe

X-ray photons, because of their long mean-free paths, can easily escape the galactic environments where they are produced, and interact at long distances with the intergalactic medium, potentially having a significant contribution to the heating and reionization of the early universe. The two most important sources of X-ray photons in the universe are active galactic nuclei (AGNs) and X-ray binaries (XRBs). In this Letter we use results from detailed, large scale population synthesis simulations to study the energy feedback of XRBs, from the first galaxies (z ∼ 20) until today. We estimate that X-ray emission from XRBs dominates over AGN at z ≳ 6-8. The shape of the spectral energy distribution of the emission from XRBs shows little change with redshift, in contrast to its normalization which evolves by ∼4 orders of magnitude, primarily due to the evolution of the cosmic star-formation rate. However, the metallicity and the mean stellar age of a given XRB population affect significantly its X-ray output. Specifically, the X-ray luminosity from high-mass XRBs per unit of star-formation rate varies an order of magnitude going from solar metallicity to less than 10% solar, and the X-ray luminosity from low-mass XRBs per unit of stellar mass peaks at an age of ∼300 Myr and then decreases gradually at later times, showing little variation for mean stellar ages ≳ 3 Gyr. Finally, we provide analytical and tabulated prescriptions for the energy output of XRBs, that can be directly incorporated in cosmological simulations. © 2013. The American Astronomical Society. All rights reserved

The X-ray-to-optical properties of optically selected active galaxiesover wide luminosity and redshift ranges

We present partial-correlation analyses that examine the strengths of the relationships between L_UV, L_X, Alpha_OX, and redshift for optically-selected AGNs. We extend the work of Strateva et al. (2005), that analyzed optically-selected AGNs from the Sloan Digital Sky Survey (SDSS), by including 52 moderate-luminosity, optically-selected AGNs from the COMBO-17 survey with corresponding deep (~250 ks to 1 Ms) X-ray observations from the Extended Chandra Deep Field-South. The COMBO-17 survey extends ~3 magnitudes deeper than the SDSS and probes the moderate-luminosity AGNs that numerically dominate the AGN population in the Universe. We also include recently published observations of 19 high-redshift, optically-selected AGNs, and 46 luminous, low-redshift AGNs from the Bright Quasar Survey. The full sample used in our analysis consists of 333 AGNs, extending out to z~6, with 293 (88%) having X-ray detections. The sample spans five decades in UV luminosity and four decades in X-ray luminosity. We confirm that Alpha_OX is strongly anti-correlated with L_UV (13.6 sigma), the highest significance found for this relation to date, and find evidence suggesting that the slope of this relation may be dependent on L_UV. We find that no significant correlation exists between Alpha_OX and redshift (1.3 sigma), and constrain the maximum evolution of AGN UV-to-X-ray flux ratios to be less than 30% (1 sigma) out to z=5. Using our sample's high X-ray detection fraction, we also find a significant anti-correlation (3.0 sigma) between Alpha_OX and L_X . We make comparisons to earlier studies on this topic and discuss implications for X-ray vs. optical luminosity functions.Comment: 16 pages, 10 figures, emulateapj. Accepted for publication in A

Young Black Hole and Neutron Star Systems in the Nearby Star-forming Galaxy M33: The NuSTAR View

Abstract We can learn about the formation and evolution of compact objects, such as neutron stars and black holes (BHs), by studying the X-ray emission from accreting systems in nearby star-forming galaxies. The hard (E &gt; 10 keV) X-ray emission in particular allows strong discrimination among the accretion states and compact object types. We conducted a NuSTAR survey (∼600 ks) of the Local Group spiral galaxy M33 to study the distribution of X-ray binary (XRB) accretors in an actively star-forming environment. We constructed color–intensity and color–color diagrams to infer XRB accretion states. Using these diagrams, we have classified 28 X-ray sources in M33 by comparing their hard X-ray colors to those of known systems. Four sources lie in the parameter space occupied by X-ray pulsars, while 8, 10, and 4 sources lie in the parameter space occupied by BHs in the hard, intermediate, and soft states, respectively. The known ultraluminous X-ray source M33 X-8 is also found to be consistent with that source type. Some sources overlap within the Z/Atoll sources due to the overlap of the two categories of BHs and Z/Atoll sources. In contrast to a similar NuSTAR survey of M31 (with a low-mass XRB-dominant population), the source population in M33 is dominated by high-mass XRBs (HMXBs), allowing the study of a very different population with similar sensitivity due to the galaxy's similar distance. This characterization of a population of HMXB accretion states will provide valuable constraints for theoretical XRB population synthesis studies to their formation and evolution.</jats:p

The population of BzK-selected ulirgs at z similar to 2

We investigate the multi-wavelength emission of BzK selected star forming galaxies at z~2 in the Great Observatories Origins Deep Survey (GOODS) North region. Most (82%) of the sources are individually detected at 24um in the Spitzer MIPS imaging, and one fourth (26%) in the VLA radio data. Significant detections of the individually undetected objects are obtained through stacking in the radio, submm and X-ray domains. The typical star forming galaxy with stellar mass ~10^{11}Mo at z=2 is an Ultra-luminous Infrared Galaxy (ULIRG), with L_IR ~ 1-2x10^{12}Lo and star formation rate SFR 200-300Mo/yr, implying a comoving density of ULIRGs at z=2 at least 3 orders of magnitude above the local one. SFRs derived from the reddening corrected UV luminosities agree well, on average, with the longer wavelength estimates. The high 24um detection rate suggests a relatively large duty cycle for the BzK star forming phase, consistently with the available independent measurements of the space density of passively evolving galaxies at z>1.4. If the IMF at z=2 is similar to the local one, and in particular is not a top-heavy IMF, this suggests that a substantial fraction of the high mass tail (>10^{11}Mo) of the galaxy stellar mass function was completed by z~1.4.Comment: 4 pages, 2 figures, ApJ Letters in pres

The extended Chandra Deep Field-South survey: Chandra point-source catalogs

We present Chandra point-source catalogs for the Extended Chandra Deep Field - South (E-CDF-S) survey. The E-CDF-S consists of four contiguous 250 ks Chandra observations covering an approximately square region of total solid angle approximate to 0.3 deg(2), which flank the existing approximate to 1 Ms Chandra Deep Field - South (CDF-S). The survey reaches sensitivity limits of approximate to 1.1 x 10(-16) and approximate to 6.7 x 10(-16) ergs cm(-2) s(-1) for the 0.5 - 2.0 and 2 - 8 keV bands, respectively. We detect 762 distinct X-ray point sources within the E-CDF-S exposure; 589 of these sources are new (i.e., not previously detected in the approximate to 1 Ms CDF-S). This brings the total number of X-ray point sources detected in the E-CDF-S region to 915 ( via the E-CDF-S and approximate to 1 Ms CDF-S observations). Source positions are determined using matched-filter and centroiding techniques; the median positional uncertainty is approximate to 0.'' 35. The basic X-ray and optical properties of these sources indicate a variety of source types, although absorbed active galactic nuclei (AGNs) seem to dominate. In addition to our main Chandra catalog, we constructed a supplementary source catalog containing 33 lower significance X-ray point sources that have bright optical counterparts ( R < 23). These sources generally have X-ray - to - optical flux ratios expected for normal and starburst galaxies, which lack a strong AGN component. We present basic number-count results for our main Chandra catalog and find good agreement with the approximate to 1 Ms CDF-S for sources with 0.5 - 2.0 and 2 - 8 keV fluxes greater than 3 x 10(-16) and 1 x 10(-15) ergs cm(-2) s(-1), respectively. Furthermore, three extended sources are detected in the 0.5 - 2.0 keV band, which are found to be likely associated with galaxy groups or poor clusters at z approximate to 0.1-0.7; these have typical rest-frame 0.5 - 2.0 keV luminosities of (1-5) x 10(42) ergs s(-1)