THE B LYMPHOCYTE DIFFERENTIATION FACTOR (BAFF) IS EXPRESSED IN THE AIRWAYS OF CHILDREN WITH CF AND IN LUNGS OF MICE INFECTED WITH PSEUDOMONAS AERUGINOSA

Background Chronic lung infection with Pseudomonas aeruginosa remains a major cause of mortality and morbidity among individuals with CF. Expression of mediators promoting recruitment and differentiation of B cells, or supporting antibody production is poorly understood yet could be key to controlling infection. Methods BAFF was measured in BAL from children with CF, both with and without P. aeruginosa, and controls. Mice were intra-nasally infected with P. aeruginosa strain LESB65 for up to 7 days. Cellular infiltration and expression of B cell chemoattractants and B cell differentiation factor, BAFF were measured in lung tissue. Results BAFF expression was elevated in both P. aeruginosa negative and positive CF patients and in P. aeruginosa infected mice post infection. Expression of the B cell chemoattractants CXCL13, CCL19 and CCL21 increased progressively post infection. Conclusions In a mouse model, infection with P. aeruginosa was associated with elevated expression of BAFF and other B cell chemoattractants suggesting a role for airway B cell recruitment and differentiation in the local adaptive immune response to P. aeruginosa. The paediatric CF airway, irrespective of pseudomonal infection, was found to be associated with an elevated level of BAFF implying that BAFF expression is not specific to pseudomonas infection and may be a feature of the CF airway. Despite the observed presence of a potent B cell activator, chronic colonisation is common suggesting that this response is ineffective

Optical Colors of Intracluster Light in the Virgo Cluster Core

We continue our deep optical imaging survey of the Virgo cluster using the CWRU Burrell Schmidt telescope by presenting B-band surface photometry of the core of the Virgo cluster in order to study the cluster's intracluster light (ICL). We find ICL features down to mu_b ~ 29 mag sq. arcsec, confirming the results of Mihos et al. (2005), who saw a vast web of low-surface brightness streams, arcs, plumes, and diffuse light in the Virgo cluster core using V-band imaging. By combining these two data sets, we are able to measure the optical colors of many of the cluster's low-surface brightness features. While much of our imaging area is contaminated by galactic cirrus, the cluster core near the cD galaxy, M87, is unobscured. We trace the color profile of M87 out to over 2000 arcsec, and find a blueing trend with radius, continuing out to the largest radii. Moreover, we have measured the colors of several ICL features which extend beyond M87's outermost reaches and find that they have similar colors to the M87's halo itself, B-V ~ 0.8. The common colors of these features suggests that the extended outer envelopes of cD galaxies, such as M87, may be formed from similar streams, created by tidal interactions within the cluster, that have since dissolved into a smooth background in the cluster potential.Comment: 14 pages. Published in ApJ, September 201

SN2008am: A Super-Luminous Type IIn Supernova

We present observations and interpretation of the Type IIn supernova SN 2008am discovered by the ROTSE Supernova Verification Project (RSVP). SN 2008am peaked at approximately -22.3 mag at a redshift of z=0.2338, giving it a peak luminosity of 3 x 10^{44}erg/s and making it one of the most luminous supernovae ever observed. The total radiated energy is ~ 2 x 10^{51} erg. Photometric observations in the ultraviolet, optical and infrared bands (J,H,Ks) constrain the SED evolution. We obtained six optical spectra of the supernova, five on the early decline from maximum light and a sixth nearly a year later plus a very late-time spectrum (~2 yr) of the host galaxy. The spectra of SN 2008am show strong Balmer-line and He I lambda 5876A emission with intermediate widths (~25A) in the first ~40 days after optical maximum. We examine a variety of models for the line wings and conclude that multiple scattering is most likely, implying that our spectra contain no specific information on the bulk flow velocity. We examine a variety of models for the ROTSE light curve subject to the rise time and the nature of the spectra, including radioactive decay, shocks in optically-thick and optically-thin circumstellar media (CSM) and a magnetar. The most successful model is one for which the CSM is optically-thick and in which diffusion of forward shock-deposited luminosity gives rise to the observed light curve. Diffusion of the shock-deposited energy from the forward shock is found to be important to account for the rising part of the light curve. Although there are differences in detail, SN 2008am appears to be closely related to other super-luminous Type IIn supernovae, SN 2006gy, SN 2006tf and perhaps SN 2008iy, that may represent the deaths of very massive LBV-type progenitors and for which the luminosity is powered by the interaction of the ejecta with a dense circumstellar medium.Comment: 58 pages, 14 figure

Evolutionary trade-offs associated with loss of PmrB function in host-adapted <i>Pseudomonas aeruginosa</i>

Pseudomonas aeruginosa colonises the upper airway of cystic fibrosis (CF) patients, providing a reservoir of host-adapted genotypes that subsequently establish chronic lung infection. We previously experimentally-evolved P. aeruginosa in a murine model of respiratory tract infection and observed early-acquired mutations in pmrB, encoding the sensor kinase of a two-component system that promoted establishment and persistence of infection. Here, using proteomics, we show downregulation of proteins involved in LPS biosynthesis, antimicrobial resistance and phenazine production in pmrB mutants, and upregulation of proteins involved in adherence, lysozyme resistance and inhibition of the chloride ion channel CFTR, relative to wild-type strain LESB65. Accordingly, pmrB mutants are susceptible to antibiotic treatment but show enhanced adherence to airway epithelial cells, resistance to lysozyme treatment, and downregulate host CFTR expression. We propose that P. aeruginosa pmrB mutations in CF patients are subject to an evolutionary trade-off, leading to enhanced colonisation potential, CFTR inhibition, and resistance to host defences, but also to increased susceptibility to antibiotics.</p

Pseudomonas aeruginosa utilises the host‐derived polyamine spermidine to facilitate antimicrobial tolerance

Pseudomonas aeruginosa undergoes diversification during infection of the cystic fibrosis (CF) lung. Understanding these changes requires model systems that capture the complexity of the CF lung environment. We previously identified loss-of-function mutations in the 2-component regulatory system sensor kinase gene pmrB in P. aeruginosa from CF lung infections and from experimental infection of mice. Here, we demonstrate that, while such mutations lowered in vitro minimum inhibitory concentrations for multiple antimicrobial classes, this was not reflected in increased antibiotic susceptibility in vivo. Loss of PmrB impaired aminoarabinose modification of LPS, increasing the negative charge of the outer membrane and promoting uptake of cationic antimicrobials. However, in vivo, this could be offset by increased membrane binding of other positively charged molecules present in lungs. The polyamine spermidine readily coated the surface of PmrB-deficient P. aeruginosa, reducing susceptibility to antibiotics that rely on charge differences to bind the outer membrane and increasing biofilm formation. Spermidine was elevated in lungs during P. aeruginosa infection in mice and during episodes of antimicrobial treatment in people with CF. These findings highlight the need to study antimicrobial resistance under clinically relevant environmental conditions. Microbial mutations carrying fitness costs in vitro may be advantageous during infection, where host resources can be utilized

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis

During experimental cerebral malaria (ECM) mice develop a lethal neuropathological syndrome associated with microcirculatory dysfunction and intravascular leukocyte sequestration. The precise spatio-temporal context in which the intravascular immune response unfolds is incompletely understood. We developed a 2-photon intravital microscopy (2P-IVM)-based brain-imaging model to monitor the real-time behaviour of leukocytes directly within the brain vasculature during ECM. Ly6Chi monocytes, but not neutrophils, started to accumulate in the blood vessels of Plasmodium berghei ANKA (PbA)-infected MacGreen mice, in which myeloid cells express GFP, one to two days prior to the onset of the neurological signs (NS). A decrease in the rolling speed of monocytes, a measure of endothelial cell activation, was associated with progressive worsening of clinical symptoms. Adoptive transfer experiments with defined immune cell subsets in recombinase activating gene (RAG)-1-deficient mice showed that these changes were mediated by Plasmodium-specific CD8+ T lymphocytes. A critical number of CD8+ T effectors was required to induce disease and monocyte adherence to the vasculature. Depletion of monocytes at the onset of disease symptoms resulted in decreased lymphocyte accumulation, suggesting reciprocal effects of monocytes and T cells on their recruitment within the brain. Together, our studies define the real-time kinetics of leukocyte behaviour in the central nervous system during ECM, and reveal a significant role for Plasmodium-specific CD8+ T lymphocytes in regulating vascular pathology in this disease. © 2014 Pai et al