The immune reconstitution inflammatory syndrome in whipple disease: a cohort study.

Whipple disease, which is caused by infection with Tropheryma whipplei, can be treated effectively with antimicrobials. Occasionally, inflammation reappears after initial improvement; this is often interpreted as refractory or recurrent disease. However, polymerase chain reaction for T. whipplei in tissue is sometimes negative during reinflammation, indicating absence of vital bacteria, and this reinflammation does not respond to antimicrobials but does respond to steroids.To demonstrate that the immune reconstitution inflammatory syndrome (IRIS) occurs in patients treated for Whipple disease.Cohort study. (International Standard Randomised Controlled Trial Number Register registration number: ISRCTN45658456)2 academic medical centers in Germany.142 patients treated for Whipple disease out of a cohort of 187 were observed for reappearance of inflammatory signs after effective antibiotic therapy. Definitions of IRIS in HIV infection, tuberculosis, and leprosy were adapted for application to Whipple disease.On the basis of study definitions, IRIS was diagnosed in 15 of 142 patients. Symptoms included fever, arthritis, pleurisy, erythema nodosum, inflammatory orbitopathy, small-bowel perforation, and a hypothalamic syndrome. Two patients died. There was a positive correlation with previous immunosuppressive treatment and a negative correlation with previous diarrhea and weight loss.The study was observational and thus has inherent weaknesses, such as incomplete and potentially selective data recording.The immune reconstitution inflammatory syndrome was diagnosed in about 10\% of patients with Whipple disease in the study cohort; the outcome varied from mild to fatal. Patients who had had previous immunosuppressive therapy were at particular risk. An immune reconstitution syndrome should be considered in patients with Whipple disease in whom inflammatory symptoms recur after effective treatment. Early diagnosis and treatment with steroids may be beneficial; prospective studies are needed.European Commission and Deutsche Forschungsgemeinschaft

Assigning a function to a conserved archaeal metallo-β-lactamase from Haloferax volcanii

The metallo-β-lactamase family of enzymes comprises a large group of proteins with diverse functions in the metabolism of the cell. Among others, this superfamily contains proteins which are involved in DNA and RNA metabolism, acting as nucleases in e.g. repair and maturation. Many proteins have been annotated in prokaryotic genomes as being potential metallo-β-lactamases, but very often the function has not been proven. The protein HVO_2763 from Haloferax volcanii is such a potential metallo-β-lactamase. HVO_2763 has sequence similarity to the metallo-β-lactamase tRNase Z, a tRNA 3′ processing endonuclease. Here, we report the characterisation of this metallo-β-lactamase HVO_2763 in the halophilic archaeon Haloferax volcanii. Using different in vitro assays with the recombinant HVO_2763, we could show that the protein does not have tRNA 3′ processing or exonuclease activity. According to transcriptome analyses of the HVO_2763 deletion strain, expression of proteins involved in membrane transport is downregulated in the mutant. Therefore, HVO_2763 might be involved directly or indirectly in membrane transport

A focus on L dwarfs with trigonometric parallaxes

This is an author-created, un-copyedited version of an article published in Publications of the Astronomical Society of the Pacific. Under embargo until 14 May 2019. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.1088/1538-3873/aaacc5.We report new parallax measurements for ten L and early T type dwarfs, five of which have no previous published values, using observations over 3 years at the robotic Liverpool Telescope. The resulting parallaxes and proper motions have median errors of 2\,mas and 1.5\,mas/year respectively. Their space motions indicate they are all Galactic disk members. We combined this sample with other objects with astrometry from the Liverpool Telescope and with published literature astrometry to construct a sample of 260 L and early T type dwarfs with measured parallaxes, designated the Astrometry Sample. We study the kinematics of the Astrometry Sample, and derived a solar motion of $(U,V,W)_{\bigodot} = (7.9\pm1.7,13.2\pm1.2,7.2\pm1.0)$\,\kms~ with respect to the local standard of rest, in agreement with recent literature. We derive a kinematic age of 1.5-1.7\,Gyr for the Astrometry Sample assuming the age increases monotonically with the total velocity for a given disk sample. This kinematic age is less than half literature values for other low mass dwarf samples. We believe this difference arises for two reasons (1) the sample is mainly composed of mid to late L dwarfs which are expected to be relatively young and (2) the requirement that objects have a measured parallax biases the sample to the brighter examples which tend to be younger.Peer reviewedFinal Accepted Versio

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery

An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks

THE RADIAL AND ROTATIONAL VELOCITIES OF PSO J318.5338-22.8603, A NEWLY CONFIRMED PLANETARY-MASS MEMBER OF THE β PICTORIS MOVING GROUP

PSO J318.5338$-$22.8603 is an extremely-red planetary-mass object that has been identified as a candidate member of the $\beta$ Pictoris moving group based on its spatial position and tangential velocity. We present a high resolution $K$-band spectrum of PSO J318.5338$-$22.8603. Using a forward-modeling Markov Chain Monte Carlo approach, we report the first measurement of the radial velocity and $v$ sin($i$) of PSO J318.5$-$22, $-$6.0$^{+0.8}_{-1.1}$ km s$^{-1}$ and 17.5$^{+2.3}_{-2.8}$ km s$^{-1}$, respectively. We calculate the space velocity and position of PSO J318.5$-$22 and confirm that it is a member of the $\beta$ Pictoris moving group. Adopting an age of 23$\pm$3 Myr for PSO J318.5$-$22, we determine a mass of $8.3\pm0.5$ $M_{\rm{Jup}}$ and effective temperature of $1127^{+24}_{-26}$ K using evolutionary models. PSO J318.5338$-$22.8603 is intermediate in mass and temperature to the directly-imaged planets $\beta$ Pictoris b and 51 Eridani b, making it an important benchmark object in the sequence of planetary-mass members of the $\beta$ Pictoris moving group. Combining our $v$ sin($i$) measurement with recent photometric variability data, we constrain the inclination of PSO J318.5$-$22 to $>29^{\circ}$ and its rotational period to 5-10.2 hours. The equatorial velocity of PSO J318.5$-$22 indicates that its rotation is consistent with an extrapolation of the velocity-mass relationship for solar system planets.Comment: 8 pages, 5 figures, 2 tables, ApJ accepte

H_2 Pure Rotational Lines in the Orion Bar

Using the Texas Echelon Cross Echelle Spectrograph (TEXES) we mapped emission in the H_2 v = 0-0 S(1) and S(2) lines toward the Orion Bar PDR at 2" resolution. We also observed H_2 v = 0-0 S(4) at selected points toward the front of the PDR. Our maps cover a 12" by 40" region of the bar where H_2 ro-vibrational lines are bright. The distributions of H_2 0-0 S(1), 0-0 S(2), and 1-0 S(1) line emission agree in remarkable detail. The high spatial resolution (0.002 pc) of our observations allows us to probe the distribution of warm gas in the Orion Bar to a distance approaching the scale length for FUV photon absorption. We use these new observational results to set parameters for the PDR models described in a companion paper (Draine et al. 2005, in prep). The best-fit model can account for the separation of the H_2 emission from the ionization front and the intensities of the ground state rotational lines as well as the 1-0 S(1) and 2-1 S(1) lines. This model requires significant adjustments to the commonly used values for the dust UV attenuation cross section and the photoelectric heating rate.Comment: 35 pages, 6 figures ApJ, accepte

UWISH2 -- The UKIRT Widefield Infrared Survey for H2

We present the goals and preliminary results of an unbiased, near-infrared, narrow-band imaging survey of the First Galactic Quadrant (10deg<l<65deg ; -1.3deg<b<+1.3deg). This area includes most of the Giant Molecular Clouds and massive star forming regions in the northern hemisphere. The survey is centred on the 1-0S(1) ro-vibrational line of H2, a proven tracer of hot, dense molecular gas in star-forming regions, around evolved stars, and in supernova remnants. The observations complement existing and upcoming photometric surveys (Spitzer-GLIMPSE, UKIDSS-GPS, JCMT-JPS, AKARI, Herschel Hi-GAL, etc.), though we probe a dynamically active component of star formation not covered by these broad-band surveys. Our narrow-band survey is currently more than 60% complete. The median seeing in our images is 0.73arcsec. The images have a 5sigma detection limit of point sources of K=18mag and the surface brightness limit is 10^-19Wm^-2arcsec^-2 when averaged over our typical seeing. Jets and outflows from both low and high mass Young Stellar Objects are revealed, as are new Planetary Nebulae and - via a comparison with earlier K-band observations acquired as part of the UKIDSS GPS - numerous variable stars. With their superior spatial resolution, the UWISH2 data also have the potential to reveal the true nature of many of the Extended Green Objects found in the GLIMPSE survey.Comment: 14pages, 8figures, 2tables, accepted for publication by MNRAS, a version with higher resolution figures can be found at http://astro.kent.ac.uk/~df

On the binary frequency of the lowest mass members of the pleiades with hubble space telescope wide field camera 3

E. V. Garcia, et al., “On the Binary Frequency of the Lowest mass Members of the Pleiades with Hubble Space Telescope Wide Field Camera 3”, The Astrophysical Journal, Vol. 804(1), May 2015. © 2015. The American Astronomical Society.We present the results of a Hubble Space Telescope Wide Field Camera 3 (WFC3) imaging survey of 11 of the lowest mass brown dwarfs in the Pleiades known (25-40 MJup). These objects represent the predecessors to T dwarfs in the field. Using a semi-empirical binary point-spread function (PSF)-fitting technique, we are able to probe to 0.″ 03 (0.75 pixel), better than 2x the WFC3/UVIS diffraction limit. We did not find any companions to our targets. From extensive testing of our PSF-fitting method on simulated binaries, we compute detection limits which rule out companions to our targets with mass ratios of 0.7 and separations 4 AU. Thus, our survey is the first to attain the high angular resolution needed to resolve brown dwarf binaries in the Pleiades at separations that are most common in the field population. We constrain the binary frequency over this range of separation and mass ratio of 25-40 MJup Pleiades brown dwarfs to bePeer reviewe