821 research outputs found

    The distribution of a germline methylation marker suggests a regional mechanism of LINE-1 silencing by the piRNA-PIWI system

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    <p>Abstract</p> <p>Background</p> <p>A defense system against transposon activity in the human germline based on PIWI proteins and piRNA has recently been discovered. It represses the activity of LINE-1 elements via DNA methylation by a largely unknown mechanism. Based on the dispersed distribution of clusters of piRNA genes in a strand-specific manner on all human chromosomes, we hypothesized that this system might work preferentially on local and proximal sequences. We tested this hypothesis with a methylation-associated SNP (mSNP) marker which is based on the density of C-T transitions in CpG dinucleotides as a surrogate marker for germline methylation.</p> <p>Results</p> <p>We found significantly higher density of mSNPs flanking piRNA clusters in the human genome for flank sizes of 1-16 Mb. A dose-response relationship between number of piRNA genes and mSNP density was found for up to 16 Mb of flanking sequences. The chromosomal density of hypermethylated LINE-1 elements had a significant positive correlation with the chromosomal density of piRNA genes (<it>r </it>= 0.41, <it>P </it>= 0.05<it>)</it>. Genome windows of 1-16 Mb containing piRNA clusters had significantly more hypermethylated LINE-1 elements than windows not containing piRNA clusters. Finally, the minimum distance to the next piRNA cluster was significantly shorter for hypermethylated LINE-1 compared to normally methylated elements (14.4 Mb vs 16.1 Mb).</p> <p>Conclusions</p> <p>Our observations support our hypothesis that the piRNA-PIWI system preferentially methylates sequences in close proximity to the piRNA clusters and perhaps physically adjacent sequences on other chromosomes. Furthermore they suggest that this proximity effect extends up to 16 Mb. This could be due to an unknown localization signal, transcription of piRNA genes near the nuclear membrane or the presence of an unknown RNA molecule that spreads across the chromosome and targets the methylation directed by the piRNA-PIWI complex. Our data suggest a region specific molecular mechanism which can be sought experimentally.</p

    Self-Organized Criticality in Compact Plasmas

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    Compact plasmas, that exist near black-hole candidates and in gamma ray burst sources, commonly exhibit self-organized non-linear behavior. A model that simulates the non-linear behavior of compact radiative plasmas is constructed directly from the observed luminosity and variability. The simulation shows that such plasmas self organize, and that the degree of non-linearity as well as the slope of the power density spectrum increase with compactness. The simulation is based on a cellular automaton table that includes the properties of the hot (relativistic) plasmas, and the magnitude of the energy perturbations. The plasmas cool or heat up, depending on whether they release more or less than the energy of a single perturbation. The energy release depends on the plasmas densities and temperatures, and the perturbations energy. Strong perturbations may cool the previously heated plasma through shocks and/or pair creation. New observations of some active galactic nuclei and gamma ray bursters are consistent with the simulationComment: 9 pages, 5 figures, AASTeX, Submitted to ApJ

    Magnetic local time dependence of geomagnetic disturbances contributing to the AU and AL indices

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    The Auroral Electrojet (AE) indices, which are composed of four indices (AU, AL, AE, and AO), are calculated from the geomagnetic field data obtained at 12 geomagnetic observatories that are located in geomagnetic latitude (GMLAT) of 61.7°-70°. The indices have been widely used to study magnetic activity in the auroral zone. In the present study, we examine magnetic local time (MLT) dependence of geomagnetic field variations contributing to the AU and AL indices. We use 1-min geomagnetic field data obtained in 2003. It is found that both AU and AL indices have two ranges of MLT (AU: 15:00-22:00MLT, ~06:00 MLT; and AL: ~02:00 MLT, 09:00-12:00 MLT) contributing to the index during quiet periods and one MLT range (AU: 15:00-20:00MLT, and AL: 00:00-06:00 MLT) during disturbed periods. These results are interpreted in terms of various ionospheric current systems, such as, Sqp, Sq, and DP2

    Electron-Positron Pairs in Hot Accretion Flows and Thin Disk Coronae

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    We investigate equilibrium accretion flows dominated by e+ee^+ e^- pairs. We consider one- and two-temperature accretion disk coronae above a thin disk, as well as hot optically thin two-temperature accretion flows without an underlying thin disk; we model the latter in the framework of advection-dominated accretion flows (ADAFs). In all three cases we include equipartition magnetic fields. We confirm the previous result that the equilibrium density of pairs in two-temperature ADAFs is negligible; and show that the inclusion of magnetic fields and the corresponding synchrotron cooling reduces the pair density even further. Similarly, we find that pairs are unimportant in two-temperature coronae. Even when the corona has significantly enhanced heating by direct transfer of viscous dissipation in the thin disk to the corona, the inefficient Coulomb coupling between protons and electrons acts as a bottleneck and prevents the high compactness required for pair-dominated solutions. Only in the case of a one-temperature corona model do we find pair-dominated thermal equilibria. These pair-dominated solutions occur over a limited range of optical depth and temperature.Comment: 38 pages, including 10 figures, LaTeX; to appear in Ap

    Increased prevalence of sleep disturbances and daytime sleepiness in subjects with bronchial asthma: a population study of young adults in three European countries

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    To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim of this study was to investigate whether asthma is associated with decreased quality of sleep and increased daytime sleepiness. The study involved a random population of 2,202 subjects supplemented by 459 subjects with suspected asthma, aged 20-45 yrs. The subjects were from Reykjavik (Iceland), Uppsala and Göteborg (Sweden) and Antwerp (Belgium), and participated in the European Community Respiratory Health Survey. The investigation included a structured interview, methacholine challenge, skinprick tests and a questionnaire on sleep disturbances. Participants in Iceland and Sweden also estimated their sleep times and made peak expiratory flow (PEF) recordings during a period of 1 week. Asthma was defined as self-reported physician-diagnosed asthma with current asthma-related symptoms (n = 267). Difficulties inducing sleep (DIS) and early morning awakenings (EMA) were about twice as common, and daytime sleepiness 50% more common, in asthmatics compared with subjects without asthma. After adjusting for possible confounders, a positive association was found between asthma and: DIS (odds ratio (OR) = 1.8); EMA (OR = 2.0); daytime sleepiness (OR = 1.6); snoring (OR = 1.7); and self reported apnoeas (OR = 3.7). Allergic rhinitis, which was reported by 71% of subjects with asthma, was independently related to DIS (OR = 2.0) and daytime sleepiness (OR = 1.3). A significant correlation was found between the number of asthma-related symptoms and sleep disturbances (p < 0.001). Asthma is associated with decreased subjective quality of sleep and increased daytime sleepiness. Concurrent allergic rhinitis may be an important underlying cause of sleep impairment in asthmatic patients

    Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature

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    Kabuki syndrome (KS) is a Mendelian Disorder of the Epigenetic Machinery (MDEM) caused by loss of function variants in either of two genes involved in the regulation of histone methylation, KMT2D (34–76%) or KDM6A (9–13%). Previously, representative neurobehavioral deficits of KS were recapitulated in a mouse model, emphasizing the role of KMT2D in brain development, specifically in ongoing hippocampal neurogenesis in the granule cell layer of the dentate gyrus. Interestingly, anxiety, a phenotype that has a known association with decreased hippocampal neurogenesis, has been anecdotally reported in individuals with KS. In this study, anxiety and behavior were assessed in a cohort of 60 individuals with molecularly confirmed KS and 25 unaffected biological siblings, via questionnaires (SCARED/GAS-ID and CBCL/ABCL). Participant age ranged from 4 to 43 years old, with 88.3% of participants having a pathogenic variant in KMT2D, and the rest having variants in KDM6A. In addition, data was collected on adaptive function and positive affect/quality of life in participants with KS using appropriate online surveys including ABAS-III and PROMIS Positive Affect. Survey scores were compared within the KS participants across age groups and between KS participants and their unaffected siblings. We found that children with KS have significantly higher anxiety scores and total behavior problem scores than their unaffected siblings (p = 0.0225, p < 0.0001). Moreover, a large proportion of affected individuals (22.2% of children and 60.0% of adults) surpassed the established threshold for anxiety; this may even be an underestimate given many patients are already treated for anxiety. In this sample, anxiety levels did not correlate with level of cognitive or adaptive function in any KS participants, but negatively correlated with positive affect in children with KS (p = 0.0005). These findings indicate that anxiety is a common neurobehavioral feature of KS. Providers should therefore carefully screen individuals with KS for anxiety as well as other behavioral issues in order to allow for prompt intervention. Neurobehavioral anxiety measures may also prove to be important outcome measures for clinical trials in KS

    A Detailed Study on the Equal Arrival Time Surface Effect in Gamma-Ray Burst Afterglows

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    Due to the relativistic motion of gamma-ray burst remnant and its deceleration in the circumburst medium, the equal arrival time surfaces at any moment are not spherical, but should be distorted ellipsoids. This will leave some imprints in the afterglows. In this article, we study the effect of equal arrival time surfaces numerically under various conditions, i.e., for isotropic fireballs, collimated jets, density jump conditions, and energy injection events. For each condition, direct comparison between the two instances when the effect is and is not included, is presented. For isotropic fireballs and jets viewed on axis, the effect slightly hardens the spectra and postpones the peak time of afterglows, but does not change the shapes of the spectra and light curves significantly. In the cases when a density jump or an energy injection is involved, the effect smears the variability of the afterglows markedly.Comment: Accepted for publication in: Chin. J. Astron. Astrophys., 15 pages, 8 embedded eps figure
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