238 research outputs found

    A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection

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    There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease- prepared siRNA) library, we isolate genes that control the recombination/endjoining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP

    Pigmentation plasticity enhances crypsis in larval newts: Associated metabolic cost and background choice behaviour

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    In heterogeneous environments, the capacity for colour change can be a valuable adaptation enhancing crypsis against predators. Alternatively, organisms might achieve concealment by evolving preferences for backgrounds that match their visual traits, thus avoiding the costs of plasticity. Here we examined the degree of plasticity in pigmentation of newt larvae (Lissotriton boscai) in relation to predation risk. Furthermore, we tested for associated metabolic costs and pigmentation-dependent background choice behaviour. Newt larvae expressed substantial changes in pigmentation so that light, high-reflecting environment induced depigmentation whereas dark, low-reflecting environment induced pigmentation in just three days of exposure. Induced pigmentation was completely reversible upon switching microhabitats. Predator cues, however, did not enhance cryptic phenotypes, suggesting that environmental albedo induces changes in pigmentation improving concealment regardless of the perceived predation risk. Metabolic rate was higher in heavily pigmented individuals from dark environments, indicating a high energetic requirement of pigmentation that could impose a constraint to larval camouflage in dim habitats. Finally, we found partial evidence for larvae selecting backgrounds matching their induced phenotypes. However, in the presence of predator cues, larvae increased the time spent in light environments, which may reflect a escape response towards shallow waters rather than an attempt at increasing crypsisFinancial support was provided by the Spanish Ministry of Science and Innovation (MICINN), Grant CGL2012-40044 to IGM, and by the Universidad AutĂłnoma de Madrid, Short Stay Grant to NPC. Additional financial support was provided by the MICINN, Grant CGL2015-68670-R to NP

    HTLV-1 infection in solid organ transplant donors and recipients in Spain

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    Background: HTLV-1 infection is a neglected disease, despite infecting 10–15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. Methods: All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. Results: A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. Conclusion: The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopath

    Rapid subacute myelopathy following kidney transplantation from HTLV-1 donors: role of immunosuppresors and failure of antiretrovirals

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    Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor-recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain

    Gaia Early Data Release 3 Acceleration of the Solar System from Gaia astrometry

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    Context. Gaia Early Data Release 3 (Gaia EDR3) provides accurate astrometry for about 1.6 million compact (QSO-like) extragalactic sources, 1.2 million of which have the best-quality five-parameter astrometric solutions. Aims. The proper motions of QSO-like sources are used to reveal a systematic pattern due to the acceleration of the solar systembarycentre with respect to the rest frame of the Universe. Apart from being an important scientific result by itself, the acceleration measured in this way is a good quality indicator of the Gaia astrometric solution. Methods. Theeffect of the acceleration was obtained as a part of the general expansion of the vector field of proper motions in vector spherical harmonics (VSH). Various versions of the VSH fit and various subsets of the sources were tried and compared to get the most consistent result and a realistic estimate of its uncertainty. Additional tests with the Gaia astrometric solution were used to get a better idea of the possible systematic errors in the estimate. Results. Our best estimate of the acceleration based on Gaia EDR3 is (2.32 +/- 0.16) x 10(-10) m s(-2) (or 7.33 +/- 0.51 km s(-1) Myr-1) towards alpha = 269.1 degrees +/- 5.4 degrees, delta = -31.6 degrees +/- 4.1 degrees, corresponding to a proper motion amplitude of 5.05 +/- 0.35 mu as yr(-1). This is in good agreement with the acceleration expected from current models of the Galactic gravitational potential. We expect that future Gaia data releases will provide estimates of the acceleration with uncertainties substantially below 0.1 mu as yr(-1).Peer reviewe

    Pulsations in main sequence OBAF-type stars

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    CONTEXT: The third Gaia data release provides photometric time series covering 34 months for about 10 million stars. For many of those stars, a characterisation in Fourier space and their variability classification are also provided. This paper focuses on intermediate- to high-mass (IHM) main sequence pulsators (M ≄  1.3 M⊙) of spectral types O, B, A, or F, known as ÎČ Cep, slowly pulsating B (SPB), ÎŽ Sct, and Îł Dor stars. These stars are often multi-periodic and display low amplitudes, making them challenging targets to analyse with sparse time series. AIMS: We investigate the extent to which the sparse Gaia DR3 data can be used to detect OBAF-type pulsators and discriminate them from other types of variables. We aim to probe the empirical instability strips and compare them with theoretical predictions. The most populated variability class is that of the ÎŽ Sct variables. For these stars, we aim to confirm their empirical period-luminosity (PL) relation, and verify the relation between their oscillation amplitude and rotation. METHODS: All datasets used in this analysis are part of the Gaia DR3 data release. The photometric time series were used to perform a Fourier analysis, while the global astrophysical parameters necessary for the empirical instability strips were taken from the Gaia DR3 gspphot tables, and the v sin i data were taken from the Gaia DR3 esphs tables. The ή Sct PL relation was derived using the same photometric parallax method as the one recently used to establish the PL relation for classical Cepheids using Gaia data. RESULTS: We show that for nearby OBAF-type pulsators, the Gaia DR3 data are precise and accurate enough to pinpoint them in the Hertzsprung-Russell (HR) diagram. We find empirical instability strips covering broader regions than theoretically predicted. In particular, our study reveals the presence of fast rotating gravity-mode pulsators outside the strips, as well as the co-existence of rotationally modulated variables inside the strips as reported before in the literature. We derive an extensive period–luminosity relation for ÎŽ Sct stars and provide evidence that the relation features different regimes depending on the oscillation period. We demonstrate how stellar rotation attenuates the amplitude of the dominant oscillation mode of ÎŽ Sct stars. CONCLUSIONS: The Gaia DR3 time-series photometry already allows for the detection of the dominant (non-)radial oscillation mode in about 100 000 intermediate- and high-mass dwarfs across the entire sky. This detection capability will increase as the time series becomes longer, allowing the additional delivery of frequencies and amplitudes of secondary pulsation modes
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