1,183 research outputs found

    Landscape of stimulation-responsive chromatin across diverse human immune cells.

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    A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells

    Zoonotic origin of the human malaria parasite Plasmodium malariae from African apes

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    The human parasite Plasmodium malariae has relatives infecting African apes (Plasmodium rodhaini) and New World monkeys (Plasmodium brasilianum), but its origins remain unknown. Using a novel approach to characterise P. malariae-related sequences in wild and captive African apes, we found that this group comprises three distinct lineages, one of which represents a previously unknown, highly divergent species infecting chimpanzees, bonobos and gorillas across central Africa. A second ape-derived lineage is much more closely related to the third, human-infective lineage P. malariae, but exhibits little evidence of genetic exchange with it, and so likely represents a separate species. Moreover, the levels and nature of genetic polymorphisms in P. malariae indicate that it resulted from the zoonotic transmission of an African ape parasite, reminiscent of the origin of P. falciparum. In contrast, P. brasilianum falls within the radiation of human P. malariae, and thus reflects a recent anthroponosis.Peer Reviewe

    Deep \u3cem\u3eChandra\u3c/em\u3e, \u3cem\u3eHST\u3c/em\u3e-Cos, and MegaCam Observations of the Phoenix Cluster: Extreme Star Formation and AGN Feedback on Hundred Kiloparsec Scales

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    We present new ultraviolet, optical, and X-ray data on the Phoenix galaxy cluster (SPT-CLJ2344-4243). Deep optical imaging reveals previously undetected filaments of star formation, extending to radii of ~50–100 kpc in multiple directions. Combined UV-optical spectroscopy of the central galaxy reveals a massive (2 x 109 M⊙), young (~4.5 Myr) population of stars, consistent with a time-averaged star formation rate of 610 ± 50 M⊙ yr−1. We report a strong detection of O ᎠÉȘ λλ1032,1038, which appears to originate primarily in shock-heated gas, but may contain a substantial contribution (\u3e1000 M⊙ yr−1) from the cooling intracluster medium (ICM). We confirm the presence of deep X-ray cavities in the inner ~10 kpc, which are among the most extreme examples of radio-mode feedback detected to date, implying jet powers of 2–7 x 1045 erg s−1. We provide evidence that the active galactic nucleus inflating these cavities may have only recently transitioned from quasar-mode to radio-mode, and may currently be insufficient to completely offset cooling. A model-subtracted residual X-ray image reveals evidence for prior episodes of strong radio-mode feedback at radii of ~100 kpc, with extended ghost cavities indicating a prior epoch of feedback roughly 100 Myr ago. This residual image also exhibits significant asymmetry in the inner ~200 kpc (0.15R500), reminiscent of infalling cool clouds, either due to minor mergers or fragmentation of the cooling ICM. Taken together, these data reveal a rapidly evolving cool core which is rich with structure (both spatially and in temperature), is subject to a variety of highly energetic processes, and yet is cooling rapidly and forming stars along thin, narrow filaments

    Performance of the X-Calibur Hard X-Ray Polarimetry Mission during its 2018/19 Long-Duration Balloon Flight

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    X-Calibur is a balloon-borne telescope that measures the polarization of high-energy X-rays in the 15--50keV energy range. The instrument makes use of the fact that X-rays scatter preferentially perpendicular to the polarization direction. A beryllium scattering element surrounded by pixellated CZT detectors is located at the focal point of the InFOC{\mu}S hard X-ray mirror. The instrument was launched for a long-duration balloon (LDB) flight from McMurdo (Antarctica) on December 29, 2018, and obtained the first constraints of the hard X-ray polarization of an accretion-powered pulsar. Here, we describe the characterization and calibration of the instrument on the ground and its performance during the flight, as well as simulations of particle backgrounds and a comparison to measured rates. The pointing system and polarimeter achieved the excellent projected performance. The energy detection threshold for the anticoincidence system was found to be higher than expected and it exhibited unanticipated dead time. Both issues will be remedied for future flights. Overall, the mission performance was nominal, and results will inform the design of the follow-up mission XL-Calibur, which is scheduled to be launched in summer 2022.Comment: 19 pages, 31 figures, submitted to Astropart. Phy

    Humic acid interferes with species recognition in zebrafish (Danio rerio)

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    Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Chemical Ecology 33 (2007): 2090-2096, doi:10.1007/s10886-007-9377-z.Few studies have addressed how chemosensation may be impaired by chemical alterations of the environment and anthropogenic disturbance. Humic acid (HA) is a pervasive, naturally occurring organic derivative found in aquatic and terrestrial environments; human activity, however, can lead to elevated levels of HA. Recent studies suggest that environments that contain high levels of HA may hinder chemical communication. We tested the ability of adult zebrafish (Danio rerio) to discriminate between conspecific and heterospecific urinary chemical cues found in the presence and absence of HA. We show that high humic acid levels (200 mg/l) can impair the ability to differentiate conspecifics from heterospecifics. We also found that zebrafish prefer untreated water over HA-treated water. These findings suggest that, in addition to human-produced synthetic compounds, changes in the abundance of naturally occurring substances may also negatively impact natural behaviors in aquatic species by disturbing the sensory environment

    Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites

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    Wild-living African apes are endemically infected with parasites that are closely related to human Plasmodium vivax, a leading cause of malaria outside Africa. This finding suggests that the origin of P. vivax was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human P. vivax and its relationship to the ape parasites, we analyzed genome sequence data of P. vivax strains infecting six chimpanzees and one gorilla from Cameroon, Gabon, and Cote d'Ivoire. We found that ape and human parasites share nearly identical core genomes, differing by only 2% of coding sequences. However, compared with the ape parasites, human strains of P. vivax exhibit about 10-fold less diversity and have a relative excess of nonsynonymous nucleotide polymorphisms, with site-frequency spectra suggesting they are subject to greatly relaxed purifying selection. These data suggest that human P. vivax has undergone an extreme bottleneck, followed by rapid population expansion. Investigating potential host-specificity determinants, we found that ape P. vivax parasites encode intact orthologs of three reticulocyte-binding protein genes (rbp2d, rbp2e, and rbp3), which are pseudogenes in all human P. vivax strains. However, binding studies of recombinant RBP2e and RBP3 proteins to human, chimpanzee, and gorilla erythrocytes revealed no evidence of host-specific barriers to red blood cell invasion. These data suggest that, from an ancient stock of P. vivax parasites capable of infecting both humans and apes, a severely bottlenecked lineage emerged out of Africa and underwent rapid population growth as it spread globally

    Discovery of X-ray polarization angle rotation in active galaxy Mrk 421

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    The magnetic field conditions in astrophysical relativistic jets can be probed by multiwavelength polarimetry, which has been recently extended to X-rays. For example, one can track how the magnetic field changes in the flow of the radiating particles by observing rotations of the electric vector position angle Κ\Psi. Here we report the discovery of a Κx\Psi_{\mathrm x} rotation in the X-ray band in the blazar Mrk 421 at an average flux state. Across the 5 days of Imaging X-ray Polarimetry Explorer (IXPE) observations of 4-6 and 7-9 June 2022, Κx\Psi_{\mathrm x} rotated in total by ≄360∘\geq360^\circ. Over the two respective date ranges, we find constant, within uncertainties, rotation rates (80±980 \pm 9 and 91±8∘/day91 \pm 8 ^\circ/\rm day) and polarization degrees (Πx=10%±1%\Pi_{\mathrm x}=10\%\pm1\%). Simulations of a random walk of the polarization vector indicate that it is unlikely that such rotation(s) are produced by a stochastic process. The X-ray emitting site does not completely overlap the radio/infrared/optical emission sites, as no similar rotation of Κ\Psi was observed in quasi-simultaneous data at longer wavelengths. We propose that the observed rotation was caused by a helical magnetic structure in the jet, illuminated in the X-rays by a localized shock propagating along this helix. The optically emitting region likely lies in a sheath surrounding an inner spine where the X-ray radiation is released
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