Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1
) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which ...suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg
(also known as Ercc5
) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1
mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1
mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of γH2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1
mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general.
We present a study of the infrared properties of X-ray selected, moderate-luminosity (i.e. L
X= 1042-1044 erg s−1) active galactic nuclei (AGNs) up to z ≈ 3, in order to explore the links between ...star formation in galaxies and accretion on to their central black holes. We use 100 and 160 μ m fluxes from GOODS-Herschel - the deepest survey yet undertaken by the Herschel telescope - and show that in the vast majority of cases (i.e. >94 per cent) these fluxes are dominated by emission from the host galaxy. As such, these far-infrared bands provide an uncontaminated view of star formation in the AGN host galaxies. We find no evidence of any correlation between the X-ray and infrared luminosities of moderate AGNs at any redshift, suggesting that global star formation is decoupled from nuclear (i.e. AGN) activity in these galaxies. On the other hand, we confirm that the star formation rates of AGN hosts increase strongly with redshift, by a factor of 43+27
− 18 from z < 0.1 to z = 2-3 for AGNs with the same range of X-ray luminosities. This increase is entirely consistent with the factor of 25-50 increase in the specific star formation rates (SSFRs) of normal, star-forming (i.e. main-sequence) galaxies over the same redshift range. Indeed, the average SSFRs of AGN hosts are only marginally (i.e. ≈20 per cent) lower than those of main-sequence galaxies at all surveyed redshifts, with this small deficit being due to a fraction of AGNs residing in quiescent (i.e. low SSFR) galaxies. We estimate that 79 ± 10 per cent of moderate-luminosity AGNs are hosted in main-sequence galaxies, 15 ± 7 per cent in quiescent galaxies and <10 per cent in strongly starbursting galaxies. We derive the fractions of all main-sequence galaxies at z < 2 that are experiencing a period of moderate nuclear activity, noting that it is strongly dependent on galaxy stellar mass (M
stars), rising from just a few per cent at M
stars∼ 1010 M⊙ to ≳20 per cent at M
stars≥ 1011 M⊙. Our results indicate that it is galaxy stellar mass that is most important in dictating whether a galaxy hosts a moderate-luminosity AGN. We argue that the majority of moderate nuclear activity is fuelled by internal mechanisms rather than violent mergers, which suggests that high-redshift disc instabilities could be an important AGN feeding mechanism.
We present the first full catalog and science results for the Nuclear Spectroscopic Telescope Array (NuSTAR) serendipitous survey. The catalog incorporates data taken during the first 40 months of ...NuSTAR operation, which provide 20 Ms of effective exposure time over 331 fields, with an areal coverage of 13 deg2, and 497 sources detected in total over the 3-24 keV energy range. There are 276 sources with spectroscopic redshifts and classifications, largely resulting from our extensive campaign of ground-based spectroscopic follow-up. We characterize the overall sample in terms of the X-ray, optical, and infrared source properties. The sample is primarily composed of active galactic nuclei (AGNs), detected over a large range in redshift from z = 0.002 to 3.4 (median of ), but also includes 16 spectroscopically confirmed Galactic sources. There is a large range in X-ray flux, from to −11, and in rest-frame 10-40 keV luminosity, from to 46, with a median of 44.1. Approximately 79% of the NuSTAR sources have lower-energy (<10 keV) X-ray counterparts from XMM-Newton, Chandra, and Swift XRT. The mid-infrared (MIR) analysis, using WISE all-sky survey data, shows that MIR AGN color selections miss a large fraction of the NuSTAR-selected AGN population, from 15% at the highest luminosities ( erg s−1) to 80% at the lowest luminosities ( erg s−1). Our optical spectroscopic analysis finds that the observed fraction of optically obscured AGNs (i.e., the type 2 fraction) is , for a well-defined subset of the 8-24 keV selected sample. This is higher, albeit at a low significance level, than the type 2 fraction measured for redshift- and luminosity-matched AGNs selected by <10 keV X-ray missions.
ABSTRACT We present the 3-8 keV and 8-24 keV number counts of active galactic nuclei (AGNs) identified in the Nuclear Spectroscopic Telescope Array (NuSTAR) extragalactic surveys. NuSTAR has now ...resolved 33%-39% of the X-ray background in the 8-24 keV band, directly identifying AGNs with obscuring columns up to . In the softer 3-8 keV band the number counts are in general agreement with those measured by XMM-Newton and Chandra over the flux range S(3-8 keV)/ probed by NuSTAR. In the hard 8-24 keV band NuSTAR probes fluxes over the range S(8-24 keV)/ , a factor ∼100 fainter than previous measurements. The 8-24 keV number counts match predictions from AGN population synthesis models, directly confirming the existence of a population of obscured and/or hard X-ray sources inferred from the shape of the integrated cosmic X-ray background. The measured NuSTAR counts lie significantly above simple extrapolation with a Euclidian slope to low flux of the Swift/BAT 15-55 keV number counts measured at higher fluxes (S(15-55 keV) 10−11 ), reflecting the evolution of the AGN population between the Swift/BAT local ( ) sample and NuSTAR's sample. CXB synthesis models, which account for AGN evolution, lie above the Swift/BAT measurements, suggesting that they do not fully capture the evolution of obscured AGNs at low redshifts.
Context. Automated arc detection methods are needed to scan the ongoing and next-generation wide-field imaging surveys, which are expected to contain thousands of strong lensing systems. Arc finders ...are also required for a quantitative comparison between predictions and observations of arc abundance. Several algorithms have been proposed to this end, but machine learning methods have remained as a relatively unexplored step in the arc finding process. Aims. In this work we introduce a new arc finder based on pattern recognition, which uses a set of morphological measurements that are derived from the Mediatrix filamentation method as entries to an artificial neural network (ANN). We show a full example of the application of the arc finder, first training and validating the ANN on simulated arcs and then applying the code on four Hubble Space Telescope (HST) images of strong lensing systems. Methods. The simulated arcs use simple prescriptions for the lens and the source, while mimicking HST observational conditions. We also consider a sample of objects from HST images with no arcs in the training of the ANN classification. We use the training and validation process to determine a suitable set of ANN configurations, including the combination of inputs from the Mediatrix method, so as to maximize the completeness while keeping the false positives low. Results. In the simulations the method was able to achieve a completeness of about 90% with respect to the arcs that are input into the ANN after a preselection. However, this completeness drops to ~ 70% on the HST images. The false detections are on the order of 3% of the objects detected in these images. Conclusions. The combination of Mediatrix measurements with an ANN is a promising tool for the pattern-recognition phase of arc finding. More realistic simulations and a larger set of real systems are needed for a better training and assessment of the efficiency of the method.
The payload of the UFFO (Ultra-Fast Flash Observatory)-pathfinder now onboard the
Lomonosov
spacecraft (hereafter UFFO/
Lomonosov
) is a dedicated instrument for the observation of GRBs. Its primary ...aim is to capture the rise phase of the optical light curve, one of the least known aspects of GRBs. Fast response measurements of the optical emission of GRB will be made by a Slewing Mirror Telescope (SMT), a key instrument of the payload, which will open a new frontier in transient studies by probing the early optical rise of GRBs with a response time in seconds for the first time. The SMT employs a rapidly slewing mirror to redirect the optical axis of the telescope to a GRB position prior determined by the UFFO Burst Alert Telescope (UBAT), the other onboard instrument, for the observation and imaging of X-rays. UFFO/Lomonosov was launched successfully from Vostochny, Russia on April 28, 2016, and will begin GRB observations after completion of functional checks of the Lomonosov spacecraft. The concept of early GRB photon measurements with UFFO was reported in 2012. In this article, we will report in detail the first mission, UFFO/Lomonosov, for the rapid response to GRB observations.
Context. A tight correlation exists between far-infrared and radio emission for star-forming galaxies (SFGs), which seems to hold out to high redshifts (z ≈ 2). Any excess of radio emission over that ...expected from star formation processes is most likely produced by an active galactic nucleus (AGN), often hidden by large amounts of dust and gas. Identifying these radio-excess sources will allow us to study a population of AGN unbiased by obscuration and thus find some of the most obscured, Compton-thick AGN, which are in large part unidentified even in the deepest X-ray and infrared (IR) surveys. Aims. We present here a new spectral energy distribution (SED) fitting approach that we adopt to select radio-excess sources amongst distant star-forming galaxies in the GOODS-Herschel (North) field and to reveal the presence of hidden, highly obscured AGN. Methods. Through extensive SED analysis of 458 galaxies with radio 1.4 GHz and mid-IR 24 μm detections using some of the deepest Chandra X-ray, Spitzer and Herschel infrared, and VLA radio data available to date, we have robustly identified a sample of 51 radio-excess AGN (~1300 deg-2) out to redshift z ≈ 3. These radio-excess AGN have a significantly lower far-IR/radio ratio (q < 1.68, 3σ) than the typical relation observed for star-forming galaxies (q ≈ 2.2). Results. We find that ≈45% of these radio-excess sources have a dominant AGN component in the mid-IR band, while for the remainders the excess radio emission is the only indicator of AGN activity. The presence of an AGN is also confirmed by the detection of a compact radio core in deep VLBI 1.4 GHz observations for eight of our radio-excess sources (≈16%; ≈66% of the VLBI detected sources in this field), with the excess radio flux measured from our SED analysis agreeing, to within a factor of two, with the radio core emission measured by VLBI. We find that the fraction of radio-excess AGN increases with X-ray luminosity reaching ~60% at LX ≈ 1044 − 1045 erg s-1, making these sources an important part of the total AGN population. However, almost half (24/51) of these radio-excess AGN are not detected in the deep Chandra X-ray data, suggesting that some of these sources might be heavily obscured. Amongst the radio-excess AGN we can distinguish three groups of objects: i) AGN clearly identified in infrared (and often in X-rays), a fraction of which are likely to be distant Compton-thick AGN; ii) moderate luminosity AGN (LX ≲ 1043 erg s-1) hosted in strong star-forming galaxies; and iii) a small fraction of low accretion-rate AGN hosted in passive (i.e. weak or no star-forming) galaxies. We also find that the specific star formation rates (sSFRs) of the radio-excess AGN are on average lower that those observed for X-ray selected AGN hosts, indicating that our sources are forming stars more slowly than typical AGN hosts, and possibly their star formation is progressively quenching.
To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study ...Terminology and Elements (APOSTEL) recommendations.
To identify studies reporting quantitative OCT results, we performed a PubMed search for the terms "quantitative" and "optical coherence tomography" from 2015 to 2017. Corresponding authors of the identified publications were invited to provide feedback on the initial APOSTEL recommendations via online surveys following the principle of a modified Delphi method. The results were evaluated and discussed by a panel of experts and changes to the initial recommendations were proposed. A final survey was recirculated among the corresponding authors to obtain a majority vote on the proposed changes.
A total of 116 authors participated in the surveys, resulting in 15 suggestions, of which 12 were finally accepted and incorporated into an updated 9-point checklist. We harmonized the nomenclature of the outer retinal layers, added the exact area of measurement to the description of volume scans, and suggested reporting device-specific features. We advised to address potential bias in manual segmentation or manual correction of segmentation errors. References to specific reporting guidelines and room light conditions were removed. The participants' consensus with the recommendations increased from 80% for the previous APOSTEL version to greater than 90%.
The modified Delphi method resulted in an expert-led guideline (evidence Class III; Grading of Recommendations, Assessment, Development and Evaluations GRADE criteria) concerning study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition analysis, nomenclature and abbreviations, and statistical approach. It will be essential to update these recommendations to new research and practices regularly.
Germ-line mutations in CYLD are found in patients with familial skin appendage tumours. The protein product functions as a deubiquitinase enzyme, which negatively regulates NF-kappaB and c-Jun ...N-terminal kinase signalling. Brooke-Spiegler syndrome (BSS) is characterised by cylindromas, trichoepitheliomas and spiradenomas, whereas in familial cylindromatosis (FC) patients present with cylindromas and in multiple familial trichoepitheliomas (MFT) with trichoepitheliomas as the only skin tumour type. Although described as distinct entities, recent studies suggest that they are within the spectrum of a single entity.
To investigate the mutation spectrum of CYLD and possible genotype-phenotype correlations.
25 families including 13 BSS, 3 FC, and 9 MFT families were examined and evaluated for mutations in the CYLD gene.
In total, 18 mutations in CYLD, including 6 novel mutations, were identified in 25 probands (72%). The mutation frequencies among distinct phenotypes were 85% for BSS, 100% for FC, and 44% for MFT. The majority of the mutations were insertions, deletions or nonsense mutations leading to formation of truncated proteins. All mutations were located between exons 9 to 20, encoding the NEMO binding site and the catalytic domain. Genotype-phenotype analysis failed to reveal a correlation between the types of mutations and their location within the gene and the patients' phenotypes and disease severity.
This study provides further evidence on the role of CYLD in the pathogenesis of skin appendage tumours characterised by cylindromas, trichoepitheliomas and/or spiradenomas, but the molecular mechanisms of CYLD in skin tumorigenesis and the reasons for phenotypic variability remain to be explored.
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