2,025 research outputs found

    Acetylation of importin-α nuclear import factors by CBP/p300.

    Get PDF
    Histone acetylases were originally identified because of their ability to acetylate histone substrates 1, 2 and 3. Acetylases can also target other proteins such as transcription factors 4, 5, 6 and 7. We asked whether the acetylase CREB-binding protein (CBP) could acetylate proteins not directly involved in transcription. A large panel of proteins, involved in a variety of cellular processes, were tested as substrates for recombinant CBP. This screen identified two proteins involved in nuclear import, Rch1 (human importin-α) and importin-α7, as targets for CBP. The acetylation site within Rch1 was mapped to a single residue, Lys22. By comparing the context of Lys22 with the sequences of other known substrates of CBP and the closely related acetylase p300, we identified G/SK (in the single-letter amino acid code) as a consensus acetylation motif. Mutagenesis of the glycine, as well as the lysine, severely impaired Rch1 acetylation, supporting the view that GK is part of a recognition motif for acetylation by CBP/p300. Using an antibody raised against an acetylated Rch1 peptide, we show that Rch1 was acetylated at Lys22 in vivo and that CBP or p300 could mediate this reaction. Lys22 lies within the binding site for a second nuclear import factor, importin-ÎČ. Acetylation of Lys22 promoted interaction with importin-ÎČ in vitro. Collectively, these results demonstrate that acetylation is not unique to proteins involved in transcription. Acetylation may regulate a variety of biological processes, including nuclear import

    The Performance and Calibration of the CRAFT Fly's Eye Fast Radio Burst Survey

    Full text link
    Since January 2017, the Commensal Real-time ASKAP Fast Transients survey (CRAFT) has been utilising commissioning antennas of the Australian SKA Pathfinder (ASKAP) to survey for fast radio bursts (FRBs) in fly's eye mode. This is the first extensive astronomical survey using phased array feeds (PAFs), and a total of 20 FRBs have been reported. Here we present a calculation of the sensitivity and total exposure of this survey, using the pulsars B1641-45 (J1644-4559) and B0833-45 (J0835-4510, i.e.\ Vela) as calibrators. The design of the survey allows us to benchmark effects due to PAF beamshape, antenna-dependent system noise, radio-frequency interference, and fluctuations during commissioning on timescales from one hour to a year. Observation time, solid-angle, and search efficiency are calculated as a function of FRB fluence threshold. Using this metric, effective survey exposures and sensitivities are calculated as a function of the source counts distribution. The implied FRB rate is significantly lower than the 3737\,sky−1^{-1}\,day−1^{-1} calculated using nominal exposures and sensitivities for this same sample by \citet{craft_nature}. At the Euclidean power-law index of −1.5-1.5, the rate is 10.7−1.8+2.7 (sys) ± 3 (stat)10.7_{-1.8}^{+2.7}\,{\rm (sys)} \, \pm \, 3\,{\rm (stat)}\,sky−1^{-1}\,day−1^{-1} above a threshold of 57±6 (sys)57\pm6\,{\rm (sys)}\,Jy\,ms, while for the best-fit index for this sample of −2.1-2.1, it is 16.6−1.5+1.9 (sys) ±4.7 (stat)16.6_{-1.5}^{+1.9} \,{\rm (sys)}\, \pm 4.7\,{\rm (stat)}\,sky−1^{-1}\,day−1^{-1} above a threshold of 41.6±1.5 (sys)41.6\pm1.5\,{\rm (sys)}\,Jy\,ms. This strongly suggests that these calculations be performed for other FRB-hunting experiments, allowing meaningful comparisons to be made between them.Comment: 21 pages, 15 figures, 2 tables, accepted for publication in PAS

    “A peculiar time in my life”: making sense of illness and recovery with gynaecological cancer

    Get PDF
    Purpose: Worldwide there are nearly 1.1 million new cases of gynaecological cancer annually. In England, uterine, ovarian and cervical cancers comprize the third most common type of new cancer in women. Research with gynaecological cancer patients within 6 months of diagnosis is rare, as is data collection that is roughly contemporaneous with treatment. Our aim was to explore the experiences of women who were, at study entry, within 6 weeks of surgery or were undergoing chemotherapy or radiotherapy. Methods: An interpretative phenomenological analysis (IPA) of data from 16 women in five focus groups was conducted in the UK, exploring women’s experiences of being diagnosed with and treated for gynaecological cancer. Results: Participants conceptualized their experiences temporally, from the shock of diagnosis, through their cancer treatment, to thinking about recovery. They tried to make sense of diagnosis, even with treatment being complete. In the context of the Self-Regulation Model, these women were struggling to interpret a changing and multi-faceted illness identity, and attempting to return to pre-illness levels of health. Conclusions: This study adds to this under-studied time period in cancer survivorship. The results suggest that survivors’ goals may change from returning to pre-illness status to reformulating goals as survival time increases.N/

    Col-OSSOS: Colors of the Interstellar Planetesimal 1I/`Oumuamua

    Get PDF
    The recent discovery by Pan-STARRS1 of 1I/2017 U1 (`Oumuamua), on an unbound and hyperbolic orbit, offers a rare opportunity to explore the planetary formation processes of other stars, and the effect of the interstellar environment on a planetesimal surface. 1I/`Oumuamua's close encounter with the inner Solar System in 2017 October was a unique chance to make observations matching those used to characterize the small-body populations of our own Solar System. We present near-simultaneous gâ€Č^\prime, râ€Č^\prime, and J photometry and colors of 1I/`Oumuamua from the 8.1-m Frederick C. Gillett Gemini North Telescope, and grigri photometry from the 4.2 m William Herschel Telescope. Our gâ€Č^\primerâ€Č^\primeJ observations are directly comparable to those from the high-precision Colours of the Outer Solar System Origins Survey (Col-OSSOS), which offer unique diagnostic information for distinguishing between outer Solar System surfaces. The J-band data also provide the highest signal-to-noise measurements made of 1I/`Oumuamua in the near-infrared. Substantial, correlated near-infrared and optical variability is present, with the same trend in both near-infrared and optical. Our observations are consistent with 1I/`Oumuamua rotating with a double-peaked period of 8.10±0.428.10 \pm 0.42 hours and being a highly elongated body with an axial ratio of at least 5.3:1, implying that it has significant internal cohesion. The color of the first interstellar planetesimal is at the neutral end of the range of Solar System g−rg-r and r−Jr-J solar-reflectance colors: it is like that of some dynamically excited objects in the Kuiper belt and the less-red Jupiter Trojans.Comment: Accepted to ApJ

    The early and late-time spectral and temporal evolution of GRB 050716

    Get PDF
    We report on a comprehensive set of observations of Gamma Ray Burst 050716, detected by the Swift satellite and subsequently followed-up rapidly in X-ray, optical and near infra-red wavebands. The prompt emission is typical of long-duration bursts, with two peaks in a time interval of T90 = 68 seconds (15 - 350 keV). The prompt emission continues at lower flux levels in the X-ray band, where several smaller flares can be seen, on top of a decaying light curve that exhibits an apparent break around 220 seconds post trigger. This temporal break is roughly coincident with a spectral break. The latter can be related to the extrapolated evolution of the break energy in the prompt gamma-ray emission, and is possibly the manifestation of the peak flux break frequency of the internal shock passing through the observing band. A possible 3 sigma change in the X-ray absorption column is also seen during this time. The late-time afterglow behaviour is relatively standard, with an electron distribution power-law index of p = 2 there is no noticable temporal break out to at least 10 days. The broad-band optical/nIR to X-ray spectrum indicates a redshift of z ~> 2 for this burst, with a host-galaxy extinction value of E(B-V) ~ 0.7 that prefers an SMC-like extinction curve.Comment: Accepted to MNRAS. 8 pages, 5 figure

    Single nucleotide polymorphisms reveal a genetic cline across the north-east Atlantic and enable powerful population assignment in the European lobster

    Get PDF
    This is the final version. Available on open access from Wiley via the DOI in this recordData Availability Statement:: Data for this study are available at the Dryad Digital Repository: https://doi.org/10.5061/dryad.2v1kr38Resolving stock structure is crucial for fisheries conservation to ensure that the spatial implementation of management is commensurate with that of biological population units. To address this in the economically important European lobster (Homarus gammarus), genetic structure was explored across the species' range using a small panel of single nucleotide polymorphisms (SNPs) previously isolated from restriction-site-associated DNA sequencing; these SNPs were selected to maximize differentiation at a range of both broad and fine scales. After quality control and filtering, 1,278 lobsters from 38 sampling sites were genotyped at 79 SNPs. The results revealed a pronounced phylogeographic break between the Atlantic and Mediterranean basins, while structure within the Mediterranean was also apparent, partitioned between lobsters from the central Mediterranean and the Aegean Sea. In addition, a genetic cline across the north-east Atlantic was revealed using both putatively neutral and outlier SNPs, but the precise driver(s) of this clinal pattern—isolation by distance, secondary contact, selection across an environmental gradient, or a combination of these factors—remains undetermined. Putatively neutral markers differentiated lobsters from Oosterschelde, an estuary on the Dutch coast, a finding likely explained by past bottlenecks and limited gene flow with adjacent North Sea populations. Building on the findings of our spatial genetic analysis, we were able to test the accuracy of assigning lobsters at various spatial scales, including to basin of origin (Atlantic or Mediterranean), region of origin and sampling location. The predictive model assembled using 79 SNPs correctly assigned 99.7% of lobsters not used to build the model to their basin of origin, but accuracy decreased to region of origin and again to sampling location. These results are of direct relevance to managers of lobster fisheries and hatcheries, and provide the basis for a genetic tool for tracing the origin of European lobsters in the food supply chain.Natural Environment Research Council (NERC)Natural EnglandUniversity of Exete

    Col-OSSOS: The Colours of the Outer Solar System Origins Survey

    Get PDF
    The Colours of the Outer Solar System Origins Survey (Col-OSSOS) is acquiring near-simultaneous gg, rr, and JJ photometry of unprecedented precision with the Gemini North Telescope, targeting nearly a hundred trans-Neptunian objects (TNOs) brighter than mr=23.6m_r=23.6 mag discovered in the Outer Solar System Origins Survey. Combining the optical and near-infrared photometry with the well-characterized detection efficiency of the Col-OSSOS target sample will provide the first flux-limited compositional dynamical map of the outer Solar System. In this paper, we describe our observing strategy and detail the data reduction processes we employ, including techniques to mitigate the impact of rotational variability. We present optical and near-infrared colors for 35 TNOs. We find two taxonomic groups for the dynamically excited TNOs, the neutral and red classes, which divide at g−r≃0.75g-r \simeq 0.75. Based on simple albedo and orbital distribution assumptions, we find that the neutral class outnumbers the red class, with a ratio of 4:1 and potentially as high as 11:1. Including in our analysis constraints from the cold classical objects, which are known to exhibit unique albedos and r−zr-z colors, we find that within our measurement uncertainty, our observations are consistent with the primordial Solar System protoplanetesimal disk being neutral-class-dominated, with two major compositional divisions in grJgrJ color space.Comment: Accepted to ApJS; on-line supplemental files will be available with the AJS published version of the pape
    • 

    corecore