Sustained striatal ciliary neurotrophic factor expression negatively affects behavior and gene expression in normal and R6/1 mice

Huntington's disease (HD) is a neurodegenerative disorder caused by an elongation of CAG repeats in the HD gene, which encodes a mutant copy of huntingtin with an expanded polyglutatmine repeat. Individuals who are affected by the disease suffer from motor, cognitive, and emotional impairments. Levels of certain striatal-enriched mRNAs decrease in both HD patients and transgenic HD mice prior to the development of motor symptoms and neuronal cell death. Ciliary neurotrophic factor (CNTF) has been shown to protect neurons against chemically induced toxic insults in vitro and in vivo. To test the hypothesis that CNTF might protect neurons from the negative effects of the mutant huntingtin protein in vivo, CNTF was continuously expressed following transduction of the striatum by recombinant adeno-associated viral vectors (rAAV2). Wild-type and R6/1 HD transgenic (R6/1) mice that received bilateral or unilateral intrastriatal injections of rAAV2-CNTF experienced weight loss. The CNTF-treated R6/1 HD transgenic mice experienced motor impairments at an earlier age than expected compared with age-matched control R6/1 HD transgenic animals. CNTF also caused abnormal behavior in WT mice. In addition to behavioral impairments, in situ hybridization showed that, in both WT and R6/1 mice, CNTF expression caused a significant decrease in the levels of striatal-enriched transcripts. Overall, continuous expression of striatal CNTF at the dose mediated by the expression cassette used in this study was detrimental to HD and wild-type mice. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58641/1/21636_ftp.pd

Precise Estimates of the Physical Parameters for the Exoplanet System HD-17156 Enabled by HST FGS Transit and Asteroseismic Observations

We present observations of three distinct transits of HD 17156b obtained with the Fine Guidance Sensors (FGS) on board the Hubble Space Telescope} (HST). We analyzed both the transit photometry and previously published radial velocities to find the planet-star radius ratio R_p/R_s = 0.07454 +/- 0.00035, inclination i=86.49 +0.24/-0.20 deg, and scaled semi-major axis a/R = 23.19 +0.32/-0.27. This last value translates directly to a mean stellar density determination of 0.522 +0.021/-0.018 g cm^-3. Analysis of asteroseismology observations by the companion paper of Gilliland et al. (2009) provides a consistent but significantly refined measurement of the stellar mean density. We compare stellar isochrones to this density estimate and find M_s = 1.275 +/- 0.018 M_sun and a stellar age of $3.37 +0.20/-0.47 Gyr. Using this estimate of M_s and incorporating the density constraint from asteroseismology, we model both the photometry and published radial velocities to estimate the planet radius R_p= 1.0870 +/- 0.0066 Jupiter radii and the stellar radius R_s = 1.5007 +/- 0.0076 R_sun. The planet radius is larger than that found in previous studies and consistent with theoretical models of a solar-composition gas giant of the same mass and equilibrium temperature. For the three transits, we determine the times of mid-transit to a precision of 6.2 s, 7.6 s, and 6.9 s, and the transit times for HD 17156 do not show any significant departures from a constant period. The joint analysis of transit photometry and asteroseismology presages similar studies that will be enabled by the NASA Kepler Mission.Comment: Accepted for publication to Ap

Viral Gene Delivery Selectively Restores Feeding and Prevents Lethality of Dopamine-Deficient Mice

AbstractDopamine-deficient mice (DA−/−), lacking tyrosine hydroxylase (TH) in dopaminergic neurons, become hypoactive and aphagic and die by 4 weeks of age. They are rescued by daily treatment with L-3,4-dihydroxyphenylalanine (L-DOPA); each dose restores dopamine (DA) and feeding for less than 24 hr. Recombinant adeno-associated viruses expressing human TH or GTP cyclohydrolase 1 (GTPCH1) were injected into the striatum of DA−/− mice. Bilateral coinjection of both viruses restored feeding behavior for several months. However, locomotor activity and coordination were partially improved. A virus expressing only TH was less effective, and one expressing GTPCH1 alone was ineffective. TH immunoreactivity and DA were detected in the ventral striatum and adjacent posterior regions of rescued mice, suggesting that these regions mediate a critical DA-dependent aspect of feeding behavior

Quaternary Stratigraphy and Stratigraphic Nomenclature Revisions in Kansas

This paper outlines Quaternary nomenclature changes to Zeller (1968) that have been adopted by the Kansas Geological Survey (KGS). The KGS formally recognizes two series/epochs for the Quaternary: the Holocene and Pleistocene. Pleistocene stage/age names Kansan, Aftonian, Nebraskan, and Yarmouthian are abandoned and replaced with the broader term "pre-Illinoian." Formation names Bignell, Peoria, Gilman Canyon, and Loveland are maintained for loess units. Formation names for the following alluvial lithostratigraphic units are abandoned: Crete, Sappa, Grand Island, Fullerton, and Holdrege. The Severance Formation is adopted as a new lithostratigraphic unit for thick packages of late Pleistocene alluvium and colluvium in Kansas. The DeForest Formation is accepted as a valid lithostratigraphic unit for deposits of fine-grained Holocene alluvium in Kansas. Formation names Iowa Point, Nickerson, and Cedar Bluffs for glacial tills and Atchison and David City for glaciofluvial deposits are abandoned. The Afton and Yarmouth Soils are abandoned as pedostratigraphic units, whereas the Sangamon Geosol and Brady Geosol are maintained

Near-infrared transit photometry of the exoplanet HD 149026b

The transiting exoplanet HD 149026b is an important case for theories of planet formation and planetary structure, because the planet's relatively small size has been interpreted as evidence for a highly metal-enriched composition. We present observations of 4 transits with the Near Infrared Camera and Multi-Object Spectrometer on the Hubble Space Telescope, within a wavelength range of 1.1--2.0 $\mu$m. Analysis of the light curve gives the most precise estimate yet of the stellar mean density, $\rho_\star = 0.497^{+0.042}_{-0.057}$ g cm$^{-3}$. By requiring agreement between the observed stellar properties (including $\rho_\star$) and stellar evolutionary models, we refine the estimate of the stellar radius: $R_\star = 1.541^{+0.046}_{-0.042}$ R_\sun. We also find a deeper transit than has been measured at optical and mid-infrared wavelengths. Taken together, these findings imply a planetary radius of $R_p = 0.813^{+0.027}_{-0.025}$ $R_{\rm Jup}$, which is larger than earlier estimates. Models of the planetary interior still require a metal-enriched composition, although the required degree of metal enrichment is reduced. It is also possible that the deeper NICMOS transit is caused by wavelength-dependent absorption by constituents in the planet's atmosphere, although simple model atmospheres do not predict this effect to be strong enough to account for the discrepancy. We use the 4 newly-measured transit times to compute a refined transit ephemeris.Comment: 18 pages, 13 figures, accepted for publication in Ap

NICMOS Observations of the Transiting Hot Jupiter XO-1b

We refine the physical parameters of the transiting hot Jupiter planet XO-1b and its stellar host XO-1 using HST NICMOS observations. XO-1b has a radius Rp=1.21+/-0.03 RJup, and XO-1 has a radius Rs=0.94+/-0.02 RSun, where the uncertainty in the mass of XO-1 dominates the uncertainty of Rp and Rs. There are no significant differences in the XO-1 system properties between these broad-band NIR observations and previous determinations based upon ground-based optical observations. We measure two transit timings from these observations with 9 s and 15 s precision. As a residual to a linear ephemeris model, there is a 2.0 sigma timing difference between the two HST visits that are separated by 3 transit events (11.8 days). These two transit timings and additional timings from the literature are sufficient to rule out the presence of an Earth mass planet orbiting in 2:1 mean motion resonance coplanar with XO-1b. We identify and correct for poorly understood gain-like variations present in NICMOS time series data. This correction reduces the effective noise in time series photometry by a factor of two, for the case of XO-1.Comment: 13 pages, 8 figures, submitted to Ap

Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage

ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2−/− mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascad

The Transit Ingress and the Tilted Orbit of the Extraordinarily Eccentric Exoplanet HD 80606b

We present the results of a transcontinental campaign to observe the 2009 June 5 transit of the exoplanet HD 80606b. We report the first detection of the transit ingress, revealing the transit duration to be 11.64 +/- 0.25 hr and allowing more robust determinations of the system parameters. Keck spectra obtained at midtransit exhibit an anomalous blueshift, giving definitive evidence that the stellar spin axis and planetary orbital axis are misaligned. The Keck data show that the projected spin-orbit angle is between 32-87 deg with 68.3% confidence and between 14-142 deg with 99.73% confidence. Thus the orbit of this planet is not only highly eccentric (e=0.93), but is also tilted away from the equatorial plane of its parent star. A large tilt had been predicted, based on the idea that the planet's eccentric orbit was caused by the Kozai mechanism. Independently of the theory, it is noteworthy that all 3 exoplanetary systems with known spin-orbit misalignments have massive planets on eccentric orbits, suggesting that those systems migrate differently than lower-mass planets on circular orbits.Comment: ApJ, in press [13 pg

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