Cell type-specific differences in β-glucan recognition and signalling in porcine innate immune cells

β-glucans exert receptor-mediated immunomodulating activities, including oxidative burst activity and cytokine secretion. The role of the β-glucan receptors dectin-1 and complement receptor 3 (CR3) in the response of immune cells towards β-glucans is still unresolved. Dectin-1 is considered as the main β-glucan receptor in mice, while recent studies in man show that CR3 is more important in β-glucan-mediated responses. This incited us to elucidate which receptor contributes to the response of innate immune cells towards particulate β-glucans in pigs as the latter might serve as a better model for man. Our results show an important role of CR3 in β-glucan recognition, as blocking this receptor strongly reduced the phagocytosis of β-glucans and the β-glucan-induced ROS production by porcine neutrophils. Conversely, dectin-1 does not seem to play a major role in β-glucan recognition in neutrophils. However, recognition of β-glucans appeared cell type-specific as both dectin-1 and CR3 are involved in the β-glucan-mediated responses in pig macrophages. Moreover, CR3 signalling through focal adhesion kinase (FAK) was indispensable for β-glucan-mediated ROS production and cytokine (TNFα, IL-1β, IL-8) production in neutrophils and macrophages, while the Syk-dependent pathway was only partly involved in these responses. We may conclude that as for man, CR3 plays a cardinal role in β-glucan signalling in porcine neutrophils, while macrophages use a more diverse receptor array to detect and respond towards β-glucans. Nonetheless, FAK acts as a master switch that regulates β-glucan-mediated responses in neutrophils as well as macrophages

Colorectal polyp outcomes after participation in the seAFOod polyp prevention trial: Evidence of rebound elevated colorectal polyp risk after short-term aspirin use

BACKGROUND: The seAFOod polyp prevention trial was a randomised, placebo-controlled, 2 × 2 factorial trial of aspirin 300 mg and eicosapentaenoic acid (EPA) 2000 mg daily in individuals who had a screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Aspirin treatment was associated with a 20% reduction in colorectal polyp number at BCSP surveillance colonoscopy 12 months later. It is unclear what happens to colorectal polyp risk after short-term aspirin use. AIM: To investigate colorectal polyp risk according to the original trial treatment allocation, up to 6 years after trial participation. METHODS: All seAFOod trial participants were scheduled for further BCSP surveillance and provided informed consent for the collection of colonoscopy outcomes. We linked BCSP colonoscopy data to trial outcomes data. RESULTS: In total, 507 individuals underwent one or more colonoscopies after trial participation. Individuals grouped by treatment allocation were well matched for clinical characteristics, follow-up duration and number of surveillance colonoscopies. The polyp detection rate (PDR; the number of individuals who had ≥1 colorectal polyp detected) after randomization to placebo aspirin was 71.1%. The PDR was 80.1% for individuals who had received aspirin (odds ratio [OR] 1.13 [95% confidence interval 1.02, 1.24]; p = 0.02). There was no difference in colorectal polyp outcomes between individuals who had been allocated to EPA compared with its placebo (OR for PDR 1.00 [0.91, 1.10]; p = 0.92). CONCLUSION: Individuals who received aspirin in the seAFOod trial demonstrated increased colorectal polyp risk during post-trial surveillance. Rebound elevated neoplastic risk after short-term aspirin use has important implications for aspirin cessation driven by age-related bleeding risk. ISRCTN05926847

Trends in anthropogenic CO2 in water masses of the Subtropical North Atlantic Ocean

12 páginas, 4 figuras,1 tabla.-- Proyecto CarbochangeThe variability in the storage of the oceanic anthropogenic CO2 (Cant) on decadal timescales is evaluated within the main water masses of the Subtropical North Atlantic along 24.5°N. Inorganic carbon measurements on five cruises of the A05 section are used to assess the changes in Cant between 1992 and 2011, using four methods (ΔC∗, TrOCA, φCT0, TTD). We find good agreement between the Cant distribution and storage obtained using chlorofluorocarbons and CO2 measurements in both the vertical and horizontal scales. Cant distribution shows higher concentrations and greater decadal storage rates in the upper layers with both values decreasing with depth. The greatest enrichment is obserbed in the central water masses, with their upper limb showing a mean annual accumulation of about 1 μmol kg−1 yr−1 and the lower limb showing, on average, half that value. We detect zonal gradients in the accumulation of Cant. This finding is less clear in the upper waters, where greater variability exists between methods. In accordance with data from time series stations, greater accumulation of Cant is observed in the upper waters of the western basin of the North Atlantic Subtropical Gyre. In intermediate and deep layers, the zonal gradient in the storage of Cant is more robust between methods. The much lower mean storage rates found along the section (<0.25 μmol kg−1 yr−1) become more obvious when longitudinal differences in the Cant accumulation are considered. In particular, west of 70°W the ventilation by the Labrador Sea Water creates a noticeable accumulation rate up to ∼0.5 μmol kg−1 yr−1 between 1000 and 2500 dbar. If a Transient Stationary State of the Cant distributions is considered, significant bi-decadal trends in the Cant storage rates in the deepest North Atlantic waters are detected, in agreement with recent estimations.We acknowledge funding from the Spanish Ministry of Economy and Competitiveness through Grants CSD2008-00077 (Circumnavigation Expedition MALASPINA 2010 Project), CTM2009-08849 (ACDC Project) and CTM2012-32017 (MANIFEST Project). We also acknowledge funding from the EU FP7 project CARBOCHANGE under Grant Agreement No. 264879 and by the Marine Biogeochemistry and Global Change research group (Generalitat de Catalunya, 2014SGR1029). E.F. Guallart was funded through a JAE-Pre grant that was financed by the Spanish National Research Council Agency (Consejo Superior de Investigaciones Científicas, CSIC) and by the European Social Fund.Peer reviewe

The SPLASH Survey: A Spectroscopic Analysis of the Metal-Poor, Low-Luminosity M31 dSph Satellite Andromeda X

Andromeda X (And X) is a newly discovered low-luminosity M31 dwarf spheroidal galaxy (dSph) found by Zucker et al. (2007) in the Sloan Digital Sky Survey (SDSS - York et al. 2000). In this paper, we present the first spectroscopic study of individual red giant branch stars in And X, as a part of the SPLASH Survey (Spectroscopic and Photometric Landscape of Andromeda's Stellar Halo). Using the Keck II telescope and multiobject DEIMOS spectrograph, we target two spectroscopic masks over the face of the galaxy and measure radial velocities for ~100 stars with a median accuracy of sigma_v ~ 3 km/s. The velocity histogram for this field confirms three populations of stars along the sight line: foreground Milky Way dwarfs at small negative velocities, M31 halo red giants over a broad range of velocities, and a very cold velocity ``spike'' consisting of 22 stars belonging to And X with v_rad = -163.8 +/- 1.2 km/s. By carefully considering both the random and systematic velocity errors of these stars (e.g., through duplicate star measurements), we derive an intrinsic velocity dispersion of just sigma_v = 3.9 +/- 1.2 km/s for And X, which for its size, implies a minimum mass-to-light ratio of M/L =37^{+26}_{-19} assuming the mass traces the light. Based on the clean sample of member stars, we measure the median metallicity of And X to be [Fe/H] = -1.93 +/- 0.11, with a slight radial metallicity gradient. The dispersion in metallicity is large, sigma([Fe/H]) = 0.48, possibly hinting that the galaxy retained much of its chemical enrichment products. We discuss the potential for better understanding the formation and evolution mechanisms for M31's system of dSphs through (current) kinematic and chemical abundance studies, especially in relation to the Milky Way sample. (abridged version)Comment: Accepted for Publication in Astrophys. J. 14 pages including 7 figures and 2 tables (journal format

Annotation of plasmid genes.

Good annotation of plasmid genomes is essential to maximise the value of the rapidly increasing volume of plasmid sequences. This short review highlights some of the current issues and suggests some ways forward. Where a well-studied related plasmid system exists we recommend that new annotation adheres to the convention already established for that system, so long as it is based on sound principles and solid experimental evidence, even if some of the new genes are more similar to homologues in different systems. Where a well-established model does not exist we provide generic gene names that reflect likely biochemical activity rather than overall purpose particularly, for example, where genes clearly belong to a type IV secretion system but it is not known whether they function in conjugative transfer or virulence. We also recommend that annotators use a whole system naming approach to avoid ending up with an illogical mixture of names from other systems based on the highest scoring match from a BLAST search. In addition, where function has not been experimentally established we recommend using just the locus tag, rather than a function-related gene name, while recording possible functions as notes rather than in a provisional name

Accretion of Planetary Material onto Host Stars

Accretion of planetary material onto host stars may occur throughout a star's life. Especially prone to accretion, extrasolar planets in short-period orbits, while relatively rare, constitute a significant fraction of the known population, and these planets are subject to dynamical and atmospheric influences that can drive significant mass loss. Theoretical models frame expectations regarding the rates and extent of this planetary accretion. For instance, tidal interactions between planets and stars may drive complete orbital decay during the main sequence. Many planets that survive their stars' main sequence lifetime will still be engulfed when the host stars become red giant stars. There is some observational evidence supporting these predictions, such as a dearth of close-in planets around fast stellar rotators, which is consistent with tidal spin-up and planet accretion. There remains no clear chemical evidence for pollution of the atmospheres of main sequence or red giant stars by planetary materials, but a wealth of evidence points to active accretion by white dwarfs. In this article, we review the current understanding of accretion of planetary material, from the pre- to the post-main sequence and beyond. The review begins with the astrophysical framework for that process and then considers accretion during various phases of a host star's life, during which the details of accretion vary, and the observational evidence for accretion during these phases.Comment: 18 pages, 5 figures (with some redacted), invited revie

Contrasting patterns of longitudinal population dynamics and antimicrobial resistance mechanisms in two priority bacterial pathogens over 7 years in a single center

Abstract: Background: Two of the most important pathogens contributing to the global rise in antimicrobial resistance (AMR) are Klebsiella pneumoniae and Enterobacter cloacae. Despite this, most of our knowledge about the changing patterns of disease caused by these two pathogens is based on studies with limited timeframes that provide few insights into their population dynamics or the dynamics in AMR elements that they can carry. Results: We investigate the population dynamics of two priority AMR pathogens over 7 years between 2007 and 2012 in a major UK hospital, spanning changes made to UK national antimicrobial prescribing policy in 2007. Between 2006 and 2012, K. pneumoniae showed epidemiological cycles of multi-drug-resistant (MDR) lineages being replaced approximately every 2 years. This contrasted E. cloacae where there was no temporally changing pattern, but a continuous presence of the mixed population. Conclusions: The differing patterns of clonal replacement and acquisition of mobile elements shows that the flux in the K. pneumoniae population was linked to the introduction of globally recognized MDR clones carrying drug resistance markers on mobile elements. However, E. cloacae carries a chromosomally encoded ampC conferring resistance to front-line treatments and shows that MDR plasmid acquisition in E. cloacae was not indicative of success in the hospital. This led to markedly different dynamics in the AMR populations of these two pathogens and shows that the mechanism of the resistance and its location in the genome or mobile elements is crucial to predict population dynamics of opportunistic pathogens in clinical settings

Lectures in Honor of the Alexander Campbell Bicentennial

In 1984, the Disciples of Christ Historical Society set forth a program to celebrate the 200th birthday of Alexander Campbell. This book launched a renewed interest in Stone-Campbell history and inspired research that shaped numerous historical projects. Contributors include T. Dwight Bozeman, Robert O. Fife, Richard L. Harrison, Samuel S. Hill, Thomas Olbricht, William J. Richardson, D. Newell Williams, Eva Jean Wrather, and Barbara Brown Zickmund.https://digitalcommons.acu.edu/acu_library_books/1018/thumbnail.jp

Observations of chemical differentiation in clumpy molecular clouds

We have extensively mapped a sample of dense molecular clouds (L1512, TMC-1C, L1262, Per 7, L1389, L1251E) in lines of HC3N, CH3OH, SO and C^{18}O. We demonstrate that a high degree of chemical differentiation is present in all of the observed clouds. We analyse the molecular maps for each cloud, demonstrating a systematic chemical differentiation across the sample, which we relate to the evolutionary state of the cloud. We relate our observations to the cloud physical, kinematical and evolutionary properties, and also compare them to the predictions of simple chemical models. The implications of this work for understanding the origin of the clumpy structures and chemical differentiation observed in dense clouds are discussed.Comment: 20 pages, 7 figures. Higher quality figures appear in the published journal articl