A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models.

Gonadotropin-releasing hormone (GnRH), a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7) neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs) are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11) neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons

The Spatial, Ionization, and Kinematic Conditions of the z=1.39 Damped Ly-alpha Absorber in Q0957+561 A,B

We examined the sizes of the absorption clouds in a z=1.3911 damped Ly-alpha absorber (DLA) in the double image lensed quasar Q0957+561 A,B (separation 135 pc at the absorber redshift). Using HIRES/Keck spectra, we studied the MgII 2796,2803 doublet, FeII multiplet, and MgI 2853 transition in absorption. We defined six "clouds" in the system of sightline A and seven clouds in the system of sightline B. An examination of the N(v) profiles, using the apparent optical depth method, reveals no clear physical connection between the clouds in A and those in B. The observed column density ratios of all clouds is log[N(MgI)/N(FeII)] ~ -2 across the full velocity range in both systems and also spatially (in both sightlines). This is a remarkable uniformity not seen in Lyman limit systems. The uniformity of the cloud properties suggests that the multiple clouds are not part of a "halo". Based upon photoionization modeling, we constrain the ionization parameters in the range -6.2 < log(U) < -5.1, where the range brackets known abundance ratio and dust depletion patterns. The inferred cloud properties are densities of 2 < n_H < 20 cm^-3, and line of sight sizes of 1 < D < 25 pc. The masses of the clouds in system A are 10 < M/M_sun < 1000 and in system B are 1 < M/M_sun < 60 for spherical clouds. For planar clouds, the upper limits are 400 M_sun and 160 M_sun for A and B, respectively. We favor a model of the absorber in which the DLA region itself is a single cloud in thiscomplex, which could be a parcel of gas in a galactic ISM. A spherical cloud of ~10 pc would be limited to one of the sightlines (A) and imply a covering factor less than 0.1 for the DLA complex. We infer that the DLA cloud properties are consistent with those of lower density, cold clouds in the Galactic interstellar medium.Comment: Accepted for publication in the Astrophysical Journal; final versio

Data calibration for the MASCARA and bRing instruments

Aims: MASCARA and bRing are photometric surveys designed to detect variability caused by exoplanets in stars with $m_V < 8.4$. Such variability signals are typically small and require an accurate calibration algorithm, tailored to the survey, in order to be detected. This paper presents the methods developed to calibrate the raw photometry of the MASCARA and bRing stations and characterizes the performance of the methods and instruments. Methods: For the primary calibration a modified version of the coarse decorrelation algorithm is used, which corrects for the extinction due to the earth's atmosphere, the camera transmission, and intrapixel variations. Residual trends are removed from the light curves of individual stars using empirical secondary calibration methods. In order to optimize these methods, as well as characterize the performance of the instruments, transit signals were injected in the data. Results: After optimal calibration an RMS scatter of 10 mmag at $m_V \sim 7.5$ is achieved in the light curves. By injecting transit signals with periods between one and five days in the MASCARA data obtained by the La Palma station over the course of one year, we demonstrate that MASCARA La Palma is able to recover 84.0, 60.5 and 20.7% of signals with depths of 2, 1 and 0.5% respectively, with a strong dependency on the observed declination, recovering 65.4% of all transit signals at $\delta > 0^\circ$ versus 35.8% at $\delta < 0^\circ$. Using the full three years of data obtained by MASCARA La Palma to date, similar recovery rates are extended to periods up to ten days. We derive a preliminary occurrence rate for hot Jupiters around A-stars of ${>} 0.4 \%$, knowing that many hot Jupiters are still overlooked. In the era of TESS, MASCARA and bRing will provide an interesting synergy for finding long-period (${>} 13.5$ days) transiting gas-giant planets around the brightest stars.Comment: 18 pages, 17 figures, accepted for publication in A&

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

Introduction to special section on the Phoenix Mission: Landing Site Characterization Experiments, Mission Overviews, and Expected Science

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94752/1/jgre2486.pd

Results from the Mars Phoenix Lander Robotic Arm experiment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95618/1/jgre2693.pd

KELT-6b: A P~7.9 d Hot Saturn Transiting a Metal-Poor Star with a Long-Period Companion

We report the discovery of KELT-6b, a mildly-inflated Saturn-mass planet transiting a metal-poor host. The initial transit signal was identified in KELT-North survey data, and the planetary nature of the occulter was established using a combination of follow-up photometry, high-resolution imaging, high-resolution spectroscopy, and precise radial velocity measurements. The fiducial model from a global analysis including constraints from isochrones indicates that the V=10.38 host star (BD+31 2447) is a mildly evolved, late-F star with T_eff=6102 \pm 43 K, log(g_*)=4.07_{-0.07}^{+0.04} and [Fe/H]=-0.28 \pm 0.04, with an inferred mass M_*=1.09 \pm 0.04 M_sun and radius R_star=1.58_{-0.09}^{+0.16} R_sun. The planetary companion has mass M_P=0.43 \pm 0.05 M_J, radius R_P=1.19_{-0.08}^{+0.13} R_J, surface gravity log(g_P)=2.86_{-0.08}^{+0.06}, and density rho_P=0.31_{-0.08}^{+0.07} g~cm^{-3}. The planet is on an orbit with semimajor axis a=0.079 \pm 0.001 AU and eccentricity e=0.22_{-0.10}^{+0.12}, which is roughly consistent with circular, and has ephemeris of T_c(BJD_TDB)=2456347.79679 \pm 0.00036 and P=7.845631 \pm 0.000046 d. Equally plausible fits that employ empirical constraints on the host star parameters rather than isochrones yield a larger planet mass and radius by ~4-7%. KELT-6b has surface gravity and incident flux similar to HD209458b, but orbits a host that is more metal poor than HD209458 by ~0.3 dex. Thus, the KELT-6 system offers an opportunity to perform a comparative measurement of two similar planets in similar environments around stars of very different metallicities. The precise radial velocity data also reveal an acceleration indicative of a longer-period third body in the system, although the companion is not detected in Keck adaptive optics images.Comment: Published in AJ, 17 pages, 15 figures, 6 table

On the Fate of Protests: Dynamics of Social Activation and Topic Selection Online and in the Streets

This chapter studies individual and network conditions for the emergence of large social protests in an agent-based model. We use two recent examples from Iran and Germany to inform the modeling process. In our agent-based model, people, who are interconnected in networks, interact and exchange their concerns on a finite number of topics. They may start to protest either because of their concern or because the fraction of protesters in their social contacts exceeds their protest threshold. In contrast to many other models of social protest, we also study the coevolution of topics of concern in the not (yet) protesting public. Given that often a small number of citizens starts a protest, its fate depends not only on the dynamics of social activation but also on the buildup of concern with respect to competing topics. Nowadays, this buildup happens decentralized through social media. The model reproduces characteristic patterns of the evolution of the two empirical cases of social protests in Iran and Germany. In particular, our results show that positions of agents with certain concern levels on certain topics within the networks are important for the fate of protests