Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis

Efficacy Of European Starling Control To Reduce Salmonella Enterica Contamination In A Concentrated Animal Feeding Operation In The Texas Panhandle

Background: European starlings (Sturnus vulgaris) are an invasive bird species known to cause damage to plant and animal agriculture. New evidence suggests starlings may also contribute to the maintenance and spread of diseases within livestock facilities. Identifying and mitigating the risk pathways that contribute to disease in livestock is necessary to reduce production losses and contamination of human food products. To better understand the impact starlings have on disease transmission to cattle we assessed the efficacy of starling control as a tool to reduce Salmonella enterica within a concentrated animal feeding operation. We matched a large facility, slated for operational control using DRC-1339 (3-chloro-4-methylaniline hydrochloride, also 3-chloro ptoluidine hydrochloride, 3-chloro-4-methylaniline), with a comparable reference facility that was not controlling birds. In both facilities, we sampled cattle feed, cattle water and cattle feces for S. enterica before and after starling control operations. Results: Within the starling-controlled CAFO, detections of S. enterica contamination disappeared from feed bunks and substantially declined within water troughs following starling control operations. Within the reference facility, detections of S. enterica contamination increased substantially within feed bunks and water troughs. Starling control was not observed to reduce prevalence of S. enterica in the cattle herd. Following starling control operations, herd prevalence of S. enterica increased on the reference facility but herd prevalence of S. enterica on the starling-controlled CAFO stayed at pretreatment levels. Conclusions: Within the starling-controlled facility detections of S. enterica disappeared from feed bunks and substantially declined within water troughs following control operations. Since cattle feed and water are obvious routes for the ingestion of S. enterica, starling control shows promise as a tool to help livestock producers manage disease. Yet, we do not believe starling control should be used as a stand alone tool to reduce S. enterica infections. Rather starling control could be used as part of a comprehensive disease management plan for concentrated animal feeding operations

Mitochondrial Stress Engages E2F1 Apoptotic Signaling to Cause Deafness

SummaryMitochondrial dysfunction causes poorly understood tissue-specific pathology stemming from primary defects in respiration, coupled with altered reactive oxygen species (ROS), metabolic signaling, and apoptosis. The A1555G mtDNA mutation that causes maternally inherited deafness disrupts mitochondrial ribosome function, in part, via increased methylation of the mitochondrial 12S rRNA by the methyltransferase mtTFB1. In patient-derived A1555G cells, we show that 12S rRNA hypermethylation causes ROS-dependent activation of AMP kinase and the proapoptotic nuclear transcription factor E2F1. This retrograde mitochondrial-stress relay is operative in vivo, as transgenic-mtTFB1 mice exhibit enhanced 12S rRNA methylation in multiple tissues, increased E2F1 and apoptosis in the stria vascularis and spiral ganglion neurons of the inner ear, and progressive E2F1-dependent hearing loss. This mouse mitochondrial disease model provides a robust platform for deciphering the complex tissue specificity of human mitochondrial-based disorders, as well as the precise pathogenic mechanism of maternally inherited deafness and its exacerbation by environmental factors.PaperFlic

Kepler-4B: A Hot Neptune-Like Planet of A G0 Star Near Main-Sequence Turnoff

Early time-series photometry from NASA's Kepler spacecraft has revealed a planet transiting the star we term Kepler-4, at R.A. = 19(h)02(m)27.(s)68, delta = +50 degrees 08'08 '' 7. The planet has an orbital period of 3.213 days and shows transits with a relative depth of 0.87 x 10(-3) and a duration of about 3.95 hr. Radial velocity (RV) measurements from the Keck High Resolution Echelle Spectrometer show a reflex Doppler signal of 9.3(-1.9)(+1.1) m s(-1), consistent with a low-eccentricity orbit with the phase expected from the transits. Various tests show no evidence for any companion star near enough to affect the light curve or the RVs for this system. From a transit-based estimate of the host star's mean density, combined with analysis of high-resolution spectra, we infer that the host star is near turnoff from the main sequence, with estimated mass and radius of 1.223(-0.091)(+0.053) M(circle dot) and 1.487(-0.084)(+0.071) R(circle dot).We estimate the planet mass and radius to be {M(P), R(P)} = {24.5 +/- 3.8 M(circle plus), 3.99 +/- 0.21 R(circle plus)}. The planet's density is near 1.9 g cm(-3); it is thus slightly denser and more massive than Neptune, but about the same size.W. M. Keck FoundationNASA's Science Mission DirectorateAstronom

The First Detection of Blue Straggler Stars in the Milky Way Bulge

We report the first detections of Blue Straggler Stars (BSS) in the bulge of the Milky Way galaxy. Proper motions from extensive space-based observations along a single sight-line allow us to separate a sufficiently clean and well-characterized bulge sample that we are able to detect a small population of bulge objects in the region of the color-magnitude diagram commonly occupied young objects and blue strgglers. However, variability measurements of these objects clearly establish that a fraction of them are blue stragglers. Out of the 42 objects found in this region of the color-magnitude diagram, we estimate that at least 18 are genuine BSS. We normalize the BSS population by our estimate of the number of horizontal branch stars in the bulge in order to compare the bulge to other stellar systems. The BSS fraction is clearly discrepant from that found in stellar clusters. The blue straggler population of dwarf spheroidals remains a subject of debate; some authors claim an anticorrelation between the normalised blue straggler fraction and integrated light. If this trend is real, then the bulge may extend it by three orders of magnitude in mass. Conversely, we find that the genuinely young (~5Gy or younger) population in the bulge, must be at most 3.4% under the most conservative scenario for the BSS population.Comment: ApJ in press; 25 pages, 6 figures, 2 table

Kepler-7b: A Transiting Planet with Unusually Low Density

We report the discovery and confirmation of Kepler-7b, a transiting planet with unusually low density. The mass is less than half that of Jupiter, Mp = 0.43 Mj, but the radius is fifty percent larger, Rp = 1.48 Rj. The resulting density, 0.17 g/cc, is the second lowest reported so far for an extrasolar planet. The orbital period is fairly long, P = 4.886 days, and the host star is not much hotter than the Sun, Teff = 6000 K. However, it is more massive and considerably larger than the sun, Mstar = 1.35 Msun and Rstar = 1.84 Rsun, and must be near the end of its life on the Main Sequence.Comment: 19 pages, 3 figure

Discovery of the Transiting Planet Kepler-5B

We present 44 days of high duty cycle, ultra precise photometry of the 13th magnitude star Kepler-5 (KIC 8191672, T(eff) = 6300 K, log g = 4.1), which exhibits periodic transits with a depth of 0.7%. Detailed modeling of the transit is consistent with a planetary companion with an orbital period of 3.548460 +/- 0.000032 days and a radius of 1.431(-0.052)(+0.041) R(J). Follow-up radial velocity measurements with the Keck HIRES spectrograph on nine separate nights demonstrate that the planet is more than twice as massive as Jupiter with a mass of 2.114(-0.059)(+0.056) M(J) and a mean density of 0.894 +/- 0.079 g cm(-3).NASA's Science Mission DirectorateAstronom

Modeling Kepler transit light curves as false positives: Rejection of blend scenarios for Kepler-9, and validation of Kepler-9d, a super-Earth-size planet in a multiple system

Light curves from the Kepler Mission contain valuable information on the nature of the phenomena producing the transit-like signals. To assist in exploring the possibility that they are due to an astrophysical false positive, we describe a procedure (BLENDER) to model the photometry in terms of a "blend" rather than a planet orbiting a star. A blend may consist of a background or foreground eclipsing binary (or star-planet pair) whose eclipses are attenuated by the light of the candidate and possibly other stars within the photometric aperture. We apply BLENDER to the case of Kepler-9, a target harboring two previously confirmed Saturn-size planets (Kepler-9b and Kepler-9c) showing transit timing variations, and an additional shallower signal with a 1.59-day period suggesting the presence of a super-Earth-size planet. Using BLENDER together with constraints from other follow-up observations we are able to rule out all blends for the two deeper signals, and provide independent validation of their planetary nature. For the shallower signal we rule out a large fraction of the false positives that might mimic the transits. The false alarm rate for remaining blends depends in part (and inversely) on the unknown frequency of small-size planets. Based on several realistic estimates of this frequency we conclude with very high confidence that this small signal is due to a super-Earth-size planet (Kepler-9d) in a multiple system, rather than a false positive. The radius is determined to be 1.64 (+0.19/-0.14) R(Earth), and current spectroscopic observations are as yet insufficient to establish its mass.Comment: 20 pages in emulateapj format, including 8 tables and 16 figures. To appear in ApJ, 1 January 2010. Accepted versio

Kepler-20: A Sun-like Star with Three Sub-Neptune Exoplanets and Two Earth-size Candidates

We present the discovery of the Kepler-20 planetary system, which we initially identified through the detection of five distinct periodic transit signals in the Kepler light curve of the host star 2MASSJ19104752+4220194. We find a stellar effective temperature Teff=5455+-100K, a metallicity of [Fe/H]=0.01+-0.04, and a surface gravity of log(g)=4.4+-0.1. Combined with an estimate of the stellar density from the transit light curves we deduce a stellar mass of Mstar=0.912+-0.034 Msun and a stellar radius of Rstar=0.944^{+0.060}_{-0.095} Rsun. For three of the transit signals, our results strongly disfavor the possibility that these result from astrophysical false positives. We conclude that the planetary scenario is more likely than that of an astrophysical false positive by a factor of 2e5 (Kepler-20b), 1e5 (Kepler-20c), and 1.1e3 (Kepler-20d), sufficient to validate these objects as planetary companions. For Kepler-20c and Kepler-20d, the blend scenario is independently disfavored by the achromaticity of the transit: From Spitzer data gathered at 4.5um, we infer a ratio of the planetary to stellar radii of 0.075+-0.015 (Kepler-20c) and 0.065+-0.011 (Kepler-20d), consistent with each of the depths measured in the Kepler optical bandpass. We determine the orbital periods and physical radii of the three confirmed planets to be 3.70d and 1.91^{+0.12}_{-0.21} Rearth for Kepler-20b, 10.85 d and 3.07^{+0.20}_{-0.31} Rearth for Kepelr-20c, and 77.61 d and 2.75^{+0.17}_{-0.30} Rearth for Kepler-20d. From multi-epoch radial velocities, we determine the masses of Kepler-20b and Kepler-20c to be 8.7\+-2.2 Mearth and 16.1+-3.5 Mearth, respectively, and we place an upper limit on the mass of Kepler-20d of 20.1 Mearth (2 sigma).Comment: accepted by ApJ, 58 pages, 12 figures revised Jan 2012 to correct table 2 and clarify planet parameter extractio