Kdo Hydrolase Is Required for Francisella tularensis Virulence and Evasion of TLR2-Mediated Innate Immunity

ABSTRACT The highly virulent Francisella tularensis subsp. tularensis has been classified as a category A bioterrorism agent. A live vaccine strain (LVS) has been developed but remains unlicensed in the United States because of an incomplete understanding of its attenuation. Lipopolysaccharide (LPS) modification is a common strategy employed by bacterial pathogens to avoid innate immunity. A novel modification enzyme has recently been identified in F. tularensis and Helicobacter pylori. This enzyme, a two-component Kdo (3-deoxy-d-manno-octulosonic acid) hydrolase, catalyzes the removal of a side chain Kdo sugar from LPS precursors. The biological significance of this modification has not yet been studied. To address the role of the two-component Kdo hydrolase KdhAB in F. tularensis pathogenesis, a ΔkdhAB deletion mutant was constructed from the LVS strain. In intranasal infection of mice, the ΔkdhAB mutant strain had a 50% lethal dose (LD50) 2 log10 units higher than that of the parental LVS strain. The levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid were significantly higher (2-fold) in mice infected with the ΔkdhAB mutant than in mice infected with LVS. In vitro stimulation of bone marrow-derived macrophages with the ΔkdhAB mutant induced higher levels of TNF-α and IL-1β in a TLR2-dependent manner. In addition, TLR2−/− mice were more susceptible than wild-type mice to ΔkdhAB bacterial infection. Finally, immunization of mice with ΔkdhAB bacteria elicited a high level of protection against the highly virulent F. tularensis subsp. tularensis strain Schu S4. These findings suggest an important role for the Francisella Kdo hydrolase system in virulence and offer a novel mutant as a candidate vaccine

The GraF instrument for imaging spectroscopy with the adaptive optics

The GraF instrument using a Fabry-Perot interferometer cross-dispersed with a grating was one of the first integral-field and long-slit spectrographs built for and used with an adaptive optics system. We describe its concept, design, optimal observational procedures and the measured performances. The instrument was used in 1997-2001 at the ESO 3.6 m telescope equipped with ADONIS adaptive optics and SHARPII+ camera. The operating spectral range was 1.2 - 2.5 microns. We used the spectral resolution from 500 to 10 000 combined with the angular resolution of 0.1" - 0.2". The quality of GraF data is illustrated by the integral field spectroscopy of the complex 0.9" x 0.9" central region of Eta Car in the 1.7 microns spectral range at the limit of spectral and angular resolutions.Comment: 36 pages, 12 figures, accepted by Ex

M Dwarfs in SDSS Stripe 82: Photometric Light Curves and Flare Rate Analysis

We present a flare rate analysis of 50,130 M dwarf light curves in SDSS Stripe 82. We identified 271 flares using a customized variability index to search ~2.5 million photometric observations for flux increases in the u- and g-bands. Every image of a flaring observation was examined by eye and with a PSF-matching and image subtraction tool to guard against false positives. Flaring is found to be strongly correlated with the appearance of H-alpha in emission in the quiet spectrum. Of the 99 flare stars that have spectra, we classify 8 as relatively inactive. The flaring fraction is found to increase strongly in stars with redder colors during quiescence, which can be attributed to the increasing flare visibility and increasing active fraction for redder stars. The flaring fraction is strongly correlated with |Z| distance such that most stars that flare are within 300 pc of the Galactic plane. We derive flare u-band luminosities and find that the most luminous flares occur on the earlier-type M dwarfs. Our best estimate of the lower limit on the flaring rate (averaged over Stripe 82) for flares with \Delta u \ge 0.7 magnitudes on stars with u < 22 is 1.3 flares hour^-1 square degree^-1 but can vary significantly with the line-of-sight.Comment: 44 pages, 13 figure

A 2.3-Day Periodic Variability in the Apparently Single Wolf-Rayet Star WR 134: Collapsed Companion or Rotational Modulation?

We present the results of an intensive campaign of spectroscopic and photometric monitoring of the peculiar Wolf-Rayet star WR 134 from 1989 to 1997. This unprecedentedly large data set allows us to confirm unambiguously the existence of a coherent 2.25 +/- 0.05 day periodicity in the line-profile changes of He II 4686, although the global pattern of variability is different from one epoch to another. This period is only marginally detected in the photometric data set. Assuming the 2.25 day periodic variability to be induced by orbital motion of a collapsed companion, we develop a simple model aiming at investigating (i) the effect of this strongly ionizing, accreting companion on the Wolf-Rayet wind structure, and (ii) the expected emergent X-ray luminosity. We argue that the predicted and observed X-ray fluxes can only be matched if the accretion on the collapsed star is significantly inhibited. Additionally, we performed simulations of line-profile variations caused by the orbital revolution of a localized, strongly ionized wind cavity surrounding the X-ray source. A reasonable fit is achieved between the observed and modeled phase-dependent line profiles of He II 4686. However, the derived size of the photoionized zone substantially exceeds our expectations, given the observed low-level X-ray flux. Alternatively, we explore rotational modulation of a persistent, largely anisotropic outflow as the origin of the observed cyclical variability. Although qualitative, this hypothesis leads to greater consistency with the observations.Comment: 34 pages, 16 figures. Accepted by the Astrophysical Journa

Spectroscopic and Spectropolarimetric Observations of V838 Mon

The spectroscopic and spectropolarimetric variability of the peculiar variable V838 Monocerotis during the brighter phases of its multiple outbursts in 2002 is presented. Significant line profile variability of H$\alpha$ and Si II 6347.10\AA & 6371.36\AA occurred in spectra obtained between 2002 February 5 and 2002 March 14, and a unique secondary absorption component was observed near the end of this time period. Our observations also suggest that multiple shifts in ionization states occurred during the outbursts. Spectropolarimetric observations reveal that V838 Mon exhibited both intrinsic and interstellar polarization components during the initial stages of the second outburst, indicating the presence of an asymmetric geometry; however, the intrinsic component had significantly declined by February 14. We determine the interstellar polarization to be $P_{max} = 2.746 \pm 0.011$, $\lambda_{max} = 5790 \pm 37\AA$, $PA = 153.43 \pm 0.12 ^{\circ}$, and we find the integrated intrinsic V band polarization on February 5 to be $P = 0.983 \pm 0.012$ at a position angle of $127.0 \pm 0.5^{\circ}$. The implications of these observations for the nature of V838 Monocerotis, its distance, and its ejecta are discussed.Comment: 20 pages (including 6 figs, 3 tables), accepted by Ap

Large-scale wind structures in OB supergiants: a search for rotationally modulated H\alpha variability

We present the results of a long-term monitoring campaign of the H\alpha line in a sample of bright OB-supergiants (O7.5-B9) that aims at detecting rotationally modulated changes potentially related to the existence of large-scale wind structures. A total of 22 objects were monitor ed during 36 nights spread over 6 months in 2001-2002. Coordinated broad-band photometric observations were also obtained for some targets. Conspicuous evidence for variability in H\alpha is found for the stars displaying a feature contaminated by wind emission. Most changes take place on a daily time-scale, although hourly variations are also occasionally detected. Convincing evidence for a cyclical pattern of variability in H\alpha has been found in 2 stars: HD 14134 and HD 42087 (periodic signals are also detected in other stars, but independent confirmation is required). Rotational modulation is suggested from the similarity between the observed recurrence time-scales (in the range 13-25 days) and estimated periods of stellar rotation. We call attention to the atypical case of HD 14134 which exhibits a clear 12.8-d periodicity both in the photometric and in the spectroscopic data sets. This places this object among a handful of early-type stars where one may observe a clear link between extended wind structures and photospheric disturbances. Further modelling may test the hypothesis that azimuthally-extended wind streams are responsible for the patterns of spectral variability in our target stars.Comment: 18 pages, accepted for publication in MNRA

Multi-epoch high-resolution spectroscopy of SN2011fe - Linking the progenitor to its environment

This study attempts to establish a link between the reasonably well known nature of the progenitor of SN2011fe and its surrounding environment. This is done with the aim of enabling the identification of similar systems in the vast majority of the cases, when distance and epoch of discovery do not allow a direct approach. To study the circumstellar environment of SN2011fe we have obtained high-resolution spectroscopy of SN2011fe on 12 epochs, from 8 to 86 days after the estimated date of explosion, targeting in particular at the time evolution of CaII and NaI. Three main absorption systems are identified from CaII and NaI, one associated to the Milky Way, one probably arising within a high-velocity cloud, and one most likely associated to the halo of M101. The Galactic and host galaxy reddening, deduced from the integrated equivalent widths (EW) of the NaI lines are E(B-V)=0.011+/-0.002 and E(B-V)=0.014+/-0.002 mag, respectively. The host galaxy absorption is dominated by a component detected at the same velocity measured from the 21-cm HI line at the projected SN position (~180 km/s). During the ~3 months covered by our observations, its EW changed by 15.6+/-6.5 mA. This small variation is shown to be compatible with the geometric effects produced by therapid SN photosphere expansion coupled to the patchy fractal structure of the ISM. The observed behavior is fully consistent with ISM properties similar to those derived for our own Galaxy, with evidences for structures on scales <100 AU. SN2011fe appears to be surrounded by a "clean" environment. The lack of blue-shifted, time-variant absorption features is fully consistent with the progenitor being a binary system with a main-sequence, or even another degenerate star.Comment: 12 pages, 6 figures, submitted to Astronomy and Astrophysic

Twenty years of stereotype threat research: A review of psychological mediators

This systematic literature review appraises critically the mediating variables of stereotype threat. A bibliographic search was conducted across electronic databases between 1995 and 2015. The search identified 45 experiments from 38 articles and 17 unique proposed mediators that were categorized into affective/subjective (n = 6), cognitive (n = 7) and motivational mechanisms (n = 4). Empirical support was accrued for mediators such as anxiety, negative thinking, and mind-wandering, which are suggested to co-opt working memory resources under stereotype threat. Other research points to the assertion that stereotype threatened individuals may be motivated to disconfirm negative stereotypes, which can have a paradoxical effect of hampering performance. However, stereotype threat appears to affect diverse social groups in different ways, with no one mediator providing unequivocal empirical support. Underpinned by the multi-threat framework, the discussion postulates that different forms of stereotype threat may be mediated by distinct mechanisms