Diesel exhaust and house dust mite allergen lead to common changes in the airway methylome and hydroxymethylome.

Exposures to diesel exhaust particles (DEP) from traffic and house dust mite (HDM) allergens significantly increase risks of airway diseases, including asthma. This negative impact of DEP and HDM may in part be mediated by epigenetic mechanisms. Beyond functioning as a mechanical barrier, airway epithelial cells provide the first line of immune defense towards DEP and HDM exposures. To understand the epigenetic responses of airway epithelial cells to these exposures, we exposed human bronchial epithelial cells to DEP and HDM and studied genome-wide 5-methyl-cytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) at base resolution. We found that exposures to DEP and HDM result in elevated TET1 and DNMT1 expression, associated with 5mC and 5hmC changes. Interestingly, over 20% of CpG sites are responsive to both exposures and changes in 5mC at these sites negatively correlated with gene expression differences. These 5mC and 5hmC changes are located in genes and pathways related to oxidative stress responses, epithelial function and immune cell responses and are enriched for binding sites of transcription factors (TFs) involved in these pathways. Histone marks associated with promoters, enhancers and actively transcribed gene bodies were associated with exposure-induced DNA methylation changes. Collectively, our data suggest that exposures to DEP and HDM alter 5mC and 5hmC levels at regulatory regions bound by TFs, which coordinate with histone marks to regulate gene networks of oxidative stress responses, epithelial function and immune cell responses. These observations provide novel insights into the epigenetic mechanisms that mediate the epithelial responses to DEP and HDM in airways

Air pollution, epigenetics, and asthma

Exposure to traffic-related air pollution (TRAP) has been implicated in asthma development, persistence, and exacerbation. This exposure is highly significant as large segments of the global population resides in zones that are most impacted by TRAP and schools are often located in high TRAP exposure areas. Recent findings shed new light on the epigenetic mechanisms by which exposure to traffic pollution may contribute to the development and persistence of asthma. In order to delineate TRAP induced effects on the epigenome, utilization of newly available innovative methods to assess and quantify traffic pollution will be needed to accurately quantify exposure. This review will summarize the most recent findings in each of these areas. Although there is considerable evidence that TRAP plays a role in asthma, heterogeneity in both the definitions of TRAP exposure and asthma outcomes has led to confusion in the field. Novel information regarding molecular characterization of asthma phenotypes, TRAP exposure assessment methods, and epigenetics are revolutionizing the field. Application of these new findings will accelerate the field and the development of new strategies for interventions to combat TRAP-induced asthma

Binary black holes in circular orbits. II. Numerical methods and first results

We present the first results from a new method for computing spacetimes representing corotating binary black holes in circular orbits. The method is based on the assumption of exact equilibrium. It uses the standard 3+1 decomposition of Einstein equations and conformal flatness approximation for the 3-metric. Contrary to previous numerical approaches to this problem, we do not solve only the constraint equations but rather a set of five equations for the lapse function, the conformal factor and the shift vector. The orbital velocity is unambiguously determined by imposing that, at infinity, the metric behaves like the Schwarzschild one, a requirement which is equivalent to the virial theorem. The numerical scheme has been implemented using multi-domain spectral methods and passed numerous tests. A sequence of corotating black holes of equal mass is calculated. Defining the sequence by requiring that the ADM mass decrease is equal to the angular momentum decrease multiplied by the orbital angular velocity, it is found that the area of the apparent horizons is constant along the sequence. We also find a turning point in the ADM mass and angular momentum curves, which may be interpreted as an innermost stable circular orbit (ISCO). The values of the global quantities at the ISCO, especially the orbital velocity, are in much better agreement with those from third post-Newtonian calculations than with those resulting from previous numerical approaches.Comment: 27 pages, 20 PostScript figures, improved presentation of the regularization procedure for the shift vector, new section devoted to the check of the momentum constraint, references added + minor corrections, accepted for publication in Phys. Rev.

No More Active Galactic Nuclei in Clumpy Disks Than in Smooth Galaxies at z~2 in CANDELS / 3D-HST

We use CANDELS imaging, 3D-HST spectroscopy, and Chandra X-ray data to investigate if active galactic nuclei (AGNs) are preferentially fueled by violent disk instabilities funneling gas into galaxy centers at 1.3<z<2.4. We select galaxies undergoing gravitational instabilities using the number of clumps and degree of patchiness as proxies. The CANDELS visual classification system is used to identify 44 clumpy disk galaxies, along with mass-matched comparison samples of smooth and intermediate morphology galaxies. We note that, despite being being mass-matched and having similar star formation rates, the smoother galaxies tend to be smaller disks with more prominent bulges compared to the clumpy galaxies. The lack of smooth extended disks is probably a general feature of the z~2 galaxy population, and means we cannot directly compare with the clumpy and smooth extended disks observed at lower redshift. We find that z~2 clumpy galaxies have slightly enhanced AGN fractions selected by integrated line ratios (in the mass-excitation method), but the spatially resolved line ratios indicate this is likely due to extended phenomena rather than nuclear AGNs. Meanwhile the X-ray data show that clumpy, smooth, and intermediate galaxies have nearly indistinguishable AGN fractions derived from both individual detections and stacked non-detections. The data demonstrate that AGN fueling modes at z~1.85 - whether violent disk instabilities or secular processes - are as efficient in smooth galaxies as they are in clumpy galaxies.Comment: ApJ accepted. 17 pages, 17 figure

Relations Between Timing Features and Colors in the X-Ray Binary 4U 0614+09

We study the correlations between timing and X-ray spectral properties in the low mass X-ray binary 4U 0614+09 using a large (265-ks) data set obtained with the Rossi X-ray Timing Explorer. We find strong quasi-periodic oscillations (QPOs) of the X-ray flux, like the kilohertz QPOs in many other X-ray binaries with accreting neutron stars, with frequencies ranging from 1329 Hz down to 418 Hz and, perhaps, as low as 153 Hz. We report the highest frequency QPO yet from any low mass X-ray binary at 1329+-4 Hz, which has implications for neutron star structure. This QPO has a 3.5-sigma single-trial significance, for an estimated 40 trials the significance is 2.4-sigma. Besides the kilohertz QPOs, the Fourier power spectra show four additional components: high frequency noise (HFN), described by a broken power-law with a break frequency between 0.7 and 45 Hz, very low frequency noise (VLFN), which is fitted as a power-law below 1 Hz, and two broad Lorentzians with centroid frequencies varying from 6 to 38 Hz and 97 to 158 Hz, respectively. We find strong correlations between the frequencies of the kilohertz QPOs, the frequency of the 6 to 38 Hz broad Lorentzian, the break frequency of the HFN, the strength of both the HFN and the VLFN and the position of the source in the hard X-ray color vs. intensity diagram. The frequency of the 97 to 158 Hz Lorentzian does not correlate with these parameters. We also find that the relation between power density and break frequency of the HFN is similar to that established for black hole candidates in the low state. We suggest that the changing mass accretion rate is responsible for the correlated changes in all these parameters.Comment: ApJ, referee

IL-9– and mast cell–mediated intestinal permeability predisposes to oral antigen hypersensitivity

Previous mouse and clinical studies demonstrate a link between Th2 intestinal inflammation and induction of the effector phase of food allergy. However, the mechanism by which sensitization and mast cell responses occurs is largely unknown. We demonstrate that interleukin (IL)-9 has an important role in this process. IL-9–deficient mice fail to develop experimental oral antigen–induced intestinal anaphylaxis, and intestinal IL-9 overexpression induces an intestinal anaphylaxis phenotype (intestinal mastocytosis, intestinal permeability, and intravascular leakage). In addition, intestinal IL-9 overexpression predisposes to oral antigen sensitization, which requires mast cells and increased intestinal permeability. These observations demonstrate a central role for IL-9 and mast cells in experimental intestinal permeability in oral antigen sensitization and suggest that IL-9–mediated mast cell responses have an important role in food allergy

Quasiequilibrium sequences of synchronized and irrotational binary neutron stars in general relativity. I. Method and tests

We present a numerical method to compute quasiequilibrium configurations of close binary neutron stars in the pre-coalescing stage. A hydrodynamical treatment is performed under the assumption that the flow is either rigidly rotating or irrotational. The latter state is technically more complicated to treat than the former one (synchronized binary), but is expected to represent fairly well the late evolutionary stages of a binary neutron star system. As regards the gravitational field, an approximation of general relativity is used, which amounts to solving five of the ten Einstein equations (conformally flat spatial metric). The obtained system of partial differential equations is solved by means of a multi-domain spectral method. Two spherical coordinate systems are introduced, one centered on each star; this results in a precise description of the stellar interiors. Thanks to the multi-domain approach, this high precision is extended to the strong field regions. The computational domain covers the whole space so that exact boundary conditions are set to infinity. Extensive tests of the numerical code are performed, including comparisons with recent analytical solutions. Finally a constant baryon number sequence (evolutionary sequence) is presented in details for a polytropic equation of state with gamma=2.Comment: Minor corrections, references updated, 42 pages, 25 PostScript figures, accepted for publication in Phys. Rev.

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz