Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Go Long, Go Deep: Finding Optical Jet Breaks for Swift-Era GRBs with the LBT

Using the 8.4m Large Binocular Telescope, we observed six GRB afterglows from 2.8 hours to 30.8 days after the burst triggers to systematically probe the late time behaviors of afterglows including jet breaks, flares, and supernova bumps. We detected five afterglows with Sloan r' magnitudes ranging from 23.0-26.3 mag. The depth of our observations allows us to extend the temporal baseline for measuring jet breaks by another decade in time scale. We detected two jet breaks and a third candidate, all of which are not detectable without deep, late time optical observations. In the other three cases, we do not detect the jet breaks either because of contamination from the host galaxy light, the presence of a supernova bump, or the intrinsic faintness of the optical afterglow. This suggests that the basic picture that GRBs are collimated is still valid and that the apparent lack of Swift jet breaks is due to poorly sampled afterglow light curves, particularly at late times.Comment: Accepted by ApJ Letters, 14 pages, 2 figure

QSO Absorption Systems Detected in Ne VIII: High-Metallicity Clouds with a Large Effective Cross Section

Using high resolution, high signal-to-noise ultraviolet spectra of the z = 0.9754 quasar PG1148+549 obtained with the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope, we study the physical conditions and abundances of NeVIII+OVI absorption line systems at z(abs) =0.68381, 0.70152, 0.72478. In addition to NeVIII and OVI, absorption lines from multiple ionization stages of oxygen (OII, OIII, OIV) are detected and are well-aligned with the more highly ionized species. We show that these absorbers are multiphase systems including hot gas (T ~ 10^{5.7} K) that produces NeVIII and OVI, and the gas metallicity of the cool phase ranges from Z = 0.3 Z_{solar} to supersolar. The cool (~10^{4} K) phases have densities n_{H} ~ 10^{-4} cm^{-3} and small sizes (< 4kpc); these cool clouds are likely to expand and dissipate, and the NeVIII may be within a transition layer between the cool gas and a surrounding, much hotter medium. The NeVIII redshift density, dN/dz = 7^{+7}_{-3}, requires a large number of these clouds for every L > 0.1L* galaxy and a large effective absorption cross section (>~ 100 kpc), and indeed, we find a star forming ~L* galaxy at the redshift of the z(abs)=0.72478 system, at an impact parameter of 217 kpc. Multiphase absorbers like these NeVIII systems are likely to be an important reservoir of baryons and metals in the circumgalactic media of galaxies.Comment: Final published version (Astrophysical Journal

The near-IR properties and continuum shapes of high redshift quasars from the Sloan Digital Sky Survey

We present J-H-K' photometry for a sample of 45 high redshift quasars found by the Sloan Digital Sky Survey. The sample was originally selected on the basis of optical colors and spans a redshift range from 3.6 to 5.03. Our photometry reflects the rest-frame SED longward of Ly alpha for all redshifts. The results show that the near-IR colors of high redshift quasars are quite uniform. We have modelled the continuum shape of the quasars (from just beyond Ly alpha to ~4000 A) with a power law of the form f_nu \propto nu^alpha, and find =-0.57 with a scatter of 0.33. This value is similar to what is found for lower redshift quasars over the same restframe wavelength range, and we conclude that there is hardly any evolution in the continuum properties of optically selected quasars up to redshift 5. The spectral indices found by combining near-IR with optical photometry are in general consistent but slightly flatter than what is found for the same quasars using the optical spectra and photometry alone, showing that the continuum region used to determine the spectral indices can somewhat influence the results.Comment: Accepted for publication in Astronomy and Astrophysic

Novel sulI binary vectors enable an inexpensive foliar selection method in Arabidopsis

<p>Abstract</p> <p>Background</p> <p>Sulfonamide resistance is conferred by the <it>sul</it>I gene found on many <it>Enterobacteriaceae </it>R plasmids and Tn21 type transposons. The <it>sul</it>I gene encodes a sulfonamide insensitive dihydropteroate synthase enzyme required for folate biosynthesis. Transformation of tobacco, potato or <it>Arabidopsis </it>using <it>sul</it>I as a selectable marker generates sulfadiazine-resistant plants. Typically <it>sul</it>I-based selection of transgenic plants is performed on tissue culture media under sterile conditions.</p> <p>Findings</p> <p>A set of novel binary vectors containing a <it>sul</it>I selectable marker expression cassette were constructed and used to generate transgenic <it>Arabidopsis</it>. We demonstrate that the <it>sul</it>I selectable marker can be utilized for direct selection of plants grown in soil with a simple foliar spray application procedure. A highly effective and inexpensive high throughput screening strategy to identify transgenic <it>Arabidopsis </it>without use of tissue culture was developed.</p> <p>Conclusion</p> <p>Novel <it>sul</it>I-containing <it>Agrobacterium </it>binary vectors designed to over-express a gene of interest or to characterize a test promoter in transgenic plants have been constructed. These new vector tools combined with the various beneficial attributes of sulfonamide selection and the simple foliar screening strategy provide an advantageous alternative for plant biotechnology researchers. The set of binary vectors is freely available upon request.</p

Chandra Survey of Radio-quiet, High-redshift Quasars

We observed 17 optically-selected, radio-quiet high-redshift quasars with the Chandra Observatory ACIS, and detected 16 of them. The quasars have redshift between 3.70 and 6.28 and include the highest redshift quasars known. When compared to low-redshift quasars observed with ROSAT, these high redshift quasars are significantly more X-ray quiet. We also find that the X-ray spectral index of the high redshift objects is flatter than the average at lower redshift. These trends confirm the predictions of models where the accretion flow is described by a cold, optically-thick accretion disk surrounded by a hot, optically thin corona, provided the viscosity parameter alpha >= 0.02. The high redshift quasars have supermassive black holes with masses ~10^{10} M_{sun}, and are accreting material at ~0.1 the Eddington limit. We detect 10 X-ray photons from the z=6.28 quasar SDS 1030+0524, which may have a Gunn-Peterson trough and be near the redshift of reionization of the intergalactic medium. The X-ray data place an upper limit on the optical depth of the intergalactic medium tau(IGM) < 10^6, compared to the lower limit from the spectrum of Lyalpha and Lybeta, which implies tau(IGM) > 20.Comment: Accepted for publication in the Astrophysical Journa

Maize ABP9 enhances tolerance to multiple stresses in transgenic Arabidopsis by modulating ABA signaling and cellular levels of reactive oxygen species

The phytohormone abscisic acid (ABA) and reactive oxygen species (ROS) play critical roles in mediating abiotic stress responses in plants. It is well known that ABA is involved in the modulation of ROS levels by regulating ROS-producing and ROS-scavenging genes, but the molecular mechanisms underlying this regulation are poorly understood. Here we show that the expression of maize ABP9 gene, which encodes a bZIP transcription factor capable of binding to the ABRE2 motif in the maize Cat1 promoter, is induced by ABA, H2O2, drought and salt. Constitutive expression of ABP9 in transgenic Arabidopsis leads to remarkably enhanced tolerance to multiple stresses including drought, high salt, freezing temperature and oxidative stresses. ABP9 expressing Arabidopsis plants also exhibit increased sensitivity to exogenously applied ABA during seed germination, root growth and stomatal closure and improved water-conserving capacity. Moreover, constitutive expression of ABP9 causes reduced cellular levels of ROS, alleviated oxidative damage and reduced cell death, accompanied by elevated expression of many stress/ABA responsive genes including those for scavenging and regulating ROS. Taken together, these results suggest that ABP9 may play a pivotal role in plant tolerance to abiotic stresses by fine tuning ABA signaling and control of ROS accumulation

A Balanced Diet Is Necessary for Proper Entrainment Signals of the Mouse Liver Clock

BACKGROUND:The peripheral circadian clock in mice is entrained not only by light-dark cycles but also by daily restricted feeding schedules. Behavioral and cell culture experiments suggest an increase in glucose level as a factor in such feeding-induced entrainment. For application of feeding-induced entrainment in humans, nutrient content and dietary variations should be considered. PRINCIPAL FINDING:To elucidate the food composition necessary for dietary entrainment, we examined whether complete or partial substitution of dietary nutrients affected phase shifts in liver clocks of mice. Compared with fasting mice or ad libitum fed mice, the liver bioluminescence rhythm advanced by 3-4 h on the middle day in Per2::luciferase knock-in mice that were administered a standard mouse diet, i.e. AIN-93M formula [0.6-0.85 g/10 g mouse BW] (composition: 14% casein, 47% cornstarch, 15% gelatinized cornstarch, 10% sugar, 4% soybean oil, and 10% other [fiber, vitamins, minerals, etc.]), for 2 days. When each nutrient was tested alone (100% nutrient), an insignificant weak phase advance was found to be induced by cornstarch and soybean oil, but almost no phase advance was induced by gelatinized cornstarch, high-amylose cornstarch, glucose, sucrose, or casein. A combination of glucose and casein without oil, vitamin, or fiber caused a significant phase advance. When cornstarch in AIN-93M was substituted with glucose, sucrose, fructose, polydextrose, high-amylose cornstarch, or gelatinized cornstarch, the amplitude of phase advance paralleled the increase in blood glucose concentration. CONCLUSIONS:Our results strongly suggest the following: (1) balanced diets containing carbohydrates/sugars and proteins are good for restricted feeding-induced entrainment of the peripheral circadian clock and (2) a balanced diet that increases blood glucose, but not by sugar alone, is suitable for entrainment. These findings may assist in the development of dietary recommendations for on-board meals served to air travelers and shift workers to reduce jet lag-like symptoms

Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

This is the final version. Available from the publisher via the DOI in this record.UK Biobank Sleep Traits GWAS summary statistics are available at the Sleep Disorder Knowledge Portal (SDKP) website (http://www.sleepdisordergenetics.org). All other data are contained within the article and its supplementary information or available upon request.Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.Medical Research Council (MRC

Terrestrial laser scanning for plot-scale forest measurement

Plot-scale measurements have been the foundation for forest surveys and reporting for over 200 years. Through recent integration with airborne and satellite remote sensing, manual measurements of vegetation structure at the plot scale are now the basis for landscape, continental and international mapping of our forest resources. The use of terrestrial laser scanning (TLS) for plot-scale measurement was first demonstrated over a decade ago, with the intimation that these instruments could replace manual measurement methods. This has not yet been the case, despite the unparalleled structural information that TLS can capture. For TLS to reach its full potential, these instruments cannot be viewed as a logical progression of existing plot-based measurement. TLS must be viewed as a disruptive technology that requires a rethink of vegetation surveys and their application across a wide range of disciplines. We review the development of TLS as a plotscale measurement tool, including the evolution of both instrument hardware and key data processing methodologies. We highlight two broad data modelling approaches of gap probability and geometrical modelling and the basic theory that underpins these. Finally, we discuss the future prospects for increasing the utilisation of TLS for plot-scale forest assessment and forest monitoring