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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.
Dynamical Architectures Of S-Type Transiting Planets In Binaries. I. Target Selection Using Hipparcos And Gaia Proper Motion Anomalies
The effect of stellar multiplicity on planetary architecture and orbital dynamics provides an important context for exoplanet demographics. We present a volume-limited catalog of up to 300 pc of 66 stars hosting planets and planet candidates from Kepler, K2, and TESS with significant Hipparcos-Gaia proper motion anomalies, which indicates the presence of companions. We assess the reliability of each transiting planet candidate using ground-based follow-up observations, and find that the TESS Objects of Interest (TOIs) with significant proper anomalies show nearly four times more false positives due to eclipsing binaries compared to TOIs with marginal proper anomalies. In addition, we find tentative evidence that orbital periods of planets orbiting TOIs with significant proper anomalies are shorter than those orbiting TOIs without significant proper anomalies, consistent with the scenario that stellar companions can truncate planet-forming disks. Furthermore, TOIs with significant proper anomalies exhibit lower Gaia differential velocities in comparison to field stars with significant proper anomalies, suggesting that planets are more likely to form in binary systems with low-mass substellar companions or stellar companions at wider separation. Finally, we characterize the three-dimensional architecture of LTT 1445 ABC using radial velocities, absolute astrometry from Gaia and Hipparcos, and relative astrometry from imaging. Our analysis reveals that LTT 1445 is a nearly flat system, with a mutual inclination of ∼2fdg88 between the orbit of BC around A and that of C around B. This coplanarity may explain why multiple planets around LTT 1445 A survive in the dynamically hostile environments of this system
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
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