360 research outputs found

    Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

    Get PDF
    Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

    Observations of the GRB Afterglow ATLAS17aeu and Its Possible Association with GW170104

    Get PDF
    We report the discovery and multiwavelength data analysis of the peculiar optical transient, ATLAS17aeu. This transient was identified in the sky map of the LIGO gravitational wave event GW 170104 by our ATLAS and Pan-STARRS coverage. ATLAS17aeu was discovered 23.1 hr after GW 170104 and rapidly faded over the next three nights, with a spectrum revealing a blue featureless continuum. The transient was also detected as a fading X-ray source by Swift and in the radio at 6 and 15 GHz. The gamma-ray burst GRB 170105A was detected by three satellites 19.04 hr after GW 170104 and 4.10 hr before our first optical detection. We analyze the multiwavelength fluxes in the context of the known GRB population and discuss the observed sky rates of GRBs and their afterglows. We find it statistically likely that ATLAS17aeu is an afterglow associated with GRB 170105A, with a chance coincidence ruled out at the 99% confidence or 2.6 sigma. A long, soft GRB within a redshift range of 1 less than or similar to z less than or similar to 2.9 would be consistent with all the observed multiwavelength data. The Poisson probability of a chance occurrence of GW 170104 and ATLAS17aeu is p = 0.04. This is the probability of a chance coincidence in 2D sky location and in time. These observations indicate that ATLAS17aeu is plausibly a normal GRB afterglow at significantly higher redshift than the distance constraint for GW 170104 and therefore a chance coincidence. However, if a redshift of the faint host were to place it within the GW 170104 distance range, then physical association with GW 170104 should be considered

    A SEARCH for AN OPTICAL COUNTERPART to the GRAVITATIONAL-WAVE EVENT GW151226

    Get PDF
    We present a search for an electromagnetic counterpart of the gravitational-wave source GW151226. Using the Pan-STARRS1 telescope we mapped out 290 square degrees in the optical iP1i_{P1} filter, starting 11.5 hr after the LIGO information release and lasting for an additional 28 days. The first observations started 49.5 hr after the time of the GW151226 detection. We typically reached sensitivity limits of iP1i_{P1} = 20.3–20.8 and covered 26.5% of the LIGO probability skymap. We supplemented this with ATLAS survey data, reaching 31% of the probability region to shallower depths of mm \simeq 19. We found 49 extragalactic transients (that are not obviously active galactic nuclei), including a faint transient in a galaxy at 7 Mpc (a luminous blue variable outburst) plus a rapidly decaying M-dwarf flare. Spectral classification of 20 other transient events showed them all to be supernovae. We found an unusual transient, PS15dpn, with an explosion date temporally coincident with GW151226, that evolved into a type Ibn supernova. The redshift of the transient is secure at zz = 0.1747 ± 0.0001 and we find it unlikely to be linked, since the luminosity distance has a negligible probability of being consistent with that of GW151226. In the 290 square degrees surveyed we therefore do not find a likely counterpart. However we show that our survey strategy would be sensitive to NS–NS mergers producing kilonovae at DLD_L \lesssim 100 Mpc, which is promising for future LIGO/Virgo searches.NASA (Grant IDs: NNX08AR22G, NNX12AR65G, NNX14AM74G, NNX12AR55G), EU/FP7-ERC (Grant IDs: 291222, 307260, 320360, 615929), a Weizmann-UK Making Connections Grant, STFC (Ernest Rutherford Fellowship), Alexander von Humboldt Foundation (Sofia Kovalevskaja Award), National Science Foundation (Grant ID: AST-1238877)This is the final version of the article. It first appeared from Institute of Physics Publishing via http://dx.doi.org/10.3847/2041-8205/827/2/L4

    Relapse to smoking during unaided cessation: Clinical, cognitive, and motivational predictors

    Get PDF
    Rationale: Neurobiological models of addiction suggest that abnormalities of brain reward circuitry distort salience attribution and inhibitory control processes, which in turn contribute to high relapse rates. Objectives: To determine whether impairments of salience attribution and inhibitory control predict relapse in a pharmacologically unaided attempt at smoking cessation. Methods: 141 smokers were assessed on indices of nicotine consumption / dependence (e.g. the FTND, cigarettes per day, salivary cotinine), and three trait impulsivity measures. After overnight abstinence they completed experimental tests of cue reactivity, attentional bias to smoking cues, response to financial reward, motor impulsiveness, and response inhibition (antisaccades). They then started a quit attempt with follow-up after 7 days, 1 month, and 3 months; abstinence was verified via salivary cotinine levels ≤ 20ng/ml. Results: Relapse rates at each point were 52.5%, 64% and 76.3%. The strongest predictor was pre-cessation salivary cotinine; other smoking / dependence indices did not explain additional outcome variance and neither did trait impulsivity. All experimental indices except responsivity to financial reward significantly predicted one week outcome. Salivary cotinine, attentional bias to smoking cues and antisaccade errors explained unique as well as shared variance. At one and three months, salivary cotinine, motor impulsiveness and cue reactivity were all individually predictive; the effects of salivary cotinine and motor impulsiveness were additive. Conclusions: These data provide some support for the involvement of abnormal cognitive and motivational processes in sustaining smoking dependence and suggest that they might be a focus of interventions, especially in the early stages of cessation. Dawkins L, Powell JH, Pickering AD, Powell JF, and West RJ (2009) Addiction 104, 850-

    ULTRA-BRIGHT OPTICAL TRANSIENTS ARE LINKED WITH TYPE Ic SUPERNOVAE

    Get PDF
    Recent searches by unbiased, wide-field surveys have uncovered a group of extremely luminous optical transients. The initial discoveries of SN 2005ap by the Texas Supernova Search and SCP-06F6 in a deep Hubble pencil beam survey were followed by the Palomar Transient Factory confirmation of host redshifts for other similar transients. The transients share the common properties of high optical luminosities (peak magnitudes ~−21 to −23), blue colors, and a lack of H or He spectral features. The physical mechanism that produces the luminosity is uncertain, with suggestions ranging from jet-driven explosion to pulsational pair instability. Here, we report the most detailed photometric and spectral coverage of an ultra-bright transient (SN 2010gx) detected in the Pan-STARRS 1 sky survey. In common with other transients in this family, early-time spectra show a blue continuum and prominent broad absorption lines of O ii. However, about 25 days after discovery, the spectra developed type Ic supernova features, showing the characteristic broad Fe ii and Si ii absorption lines. Detailed, post-maximum follow-up may show that all SN 2005ap and SCP-06F6 type transients are linked to supernovae Ic. This poses problems in understanding the physics of the explosions: there is no indication from late-time photometry that the luminosity is powered by 56Ni, the broad light curves suggest very large ejected masses, and the slow spectral evolution is quite different from typical Ic timescales. The nature of the progenitor stars and the origin of the luminosity are intriguing and open questions

    Pan-STARRS and PESSTO search for an optical counterpart to the LIGO gravitational-wave source GW150914

    Get PDF
    This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw1893We searched for an optical counterpart to the first gravitational wave source discovered by LIGO (GW150914), using a combination of the Pan-STARRS1 wide-field telescope and the PESSTO spectroscopic follow-up programme. As the final LIGO sky maps changed during analysis, the total probability of the source being spatially coincident with our fields was finally only 4.2 per cent. Therefore we discuss our results primarily as a demonstration of the survey capability of Pan-STARRS and spectroscopic capability of PESSTO. We mapped out 442 square degrees of the northern sky region of the initial map. We discovered 56 astrophysical transients over a period of 41 days from the discovery of the source. Of these, 19 were spectroscopically classified and a further 13 have host galaxy redshifts. All transients appear to be fairly normal supernovae and AGN variability and none is obviously linked with GW150914. We illustrate the sensitivity of our survey by defining parameterised lightcurves with timescales of 4, 20 and 40 days and use the sensitivity of the Pan-STARRS1 images to set limits on the luminosities of possible sources. The Pan-STARRS1 images reach limiting magnitudes of i\textit{i}P_{P\rceil} = 19.2, 20.0 and 20.8 respectively for the three timescales. For long timescale parameterised lightcurves (with FWHM≃40d) we set upper limits of M\textit{M}i_{i} ≤ −17.2+1.40.9^{−0.9}_{+1.4} if the distance to GW150914 is D\textit{D}_{\lfloor} = 400 ± 200 Mpc. The number of type Ia SN we find in the survey is similar to that expected from the cosmic SN rate, indicating a reasonably complete efficiency in recovering supernova like transients out to D\textit{D}_{\lfloor} = 400 ± 200 Mpc.Pan-STARRS is supported by the University of Hawaii and the National Aeronautics and Space Administration's Planetary Defense Office under Grant No. NNX14AM74G. The Pan-STARRS-LIGO effort is in collaboration with the LIGO Consortium and supported by Queen's University Belfast. The Pan-STARRS1 Sky Surveys have been made possible through contributions by the Institute for Astronomy, the University of Hawaii, the Pan-STARRS Project Office, the Max Planck Society and its participating institutes, the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching, The Johns Hopkins University, Durham University, the University of Edinburgh, the Queen's University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated, the National Central University of Taiwan, the Space Telescope Science Institute, and the National Aeronautics and Space Administration under Grant No. NNX08AR22G issued through the Planetary Science Division of the NASA Science Mission Directorate, the National Science Foundation Grant No. AST-1238877, the University of Maryland, Eotvos Lorand University (ELTE), and the Los Alamos National Laboratory. This work is based (in part) on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile as part of PESSTO, (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO programs 188.D-3003, 191.D-0935. Some of the data presented herein were obtained at the Palomar Observatory, California Institute of Technology. SJS acknowledges funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no [291222] and STFC grants ST/I001123/1 and ST/L000709/1. MF is supported by the European Union FP7 programme through ERC grant number 320360. KM acknowledges support from the STFC through an Ernest Rutherford Fellowship FOE acknowledges support from FONDECYT through postdoctoral grant 3140326. This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration and data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation

    SdiA, an N-Acylhomoserine Lactone Receptor, Becomes Active during the Transit of Salmonella enterica through the Gastrointestinal Tract of Turtles

    Get PDF
    encode a LuxR-type AHL receptor, SdiA, they cannot synthesize AHLs. In vitro, it is known that SdiA can detect AHLs produced by other bacterial species..We conclude that the normal gastrointestinal microbiota of most animal species do not produce AHLs of the correct type, in an appropriate location, or in sufficient quantities to activate SdiA. However, the results obtained with turtles represent the first demonstration of SdiA activity in animals
    corecore