CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2

The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1−/− mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1−/− peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam2CSK4 and to HSV-1. CD200R1−/− macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1−/− mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1−/− mice and CD200R1−/− fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence

CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2

The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1−/− mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1−/− peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam2CSK4 and to HSV-1. CD200R1−/− macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1−/− mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1−/− mice and CD200R1−/− fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence

Pilot-WINGS: An extended MUSE view of the structure of Abell 370

We investigate the strong-lensing cluster Abell 370 (A370) using a wide Integral Field Unit (IFU) spectroscopic mosaic from the Multi-Unit Spectroscopic Explorer (MUSE). IFU spectroscopy provides significant insight into the structure and mass content of galaxy clusters, yet IFU-based cluster studies focus almost exclusively on the central Einstein-radius region. Covering over 14 arcmin2, the new MUSE mosaic extends significantly beyond the A370 Einstein radius, providing, for the first time, a detailed look at the cluster outskirts. Combining these data with wide-field, multi-band Hubble Space Telescope (HST) imaging from the BUFFALO project, we analyse the distribution of objects within the cluster and along the line of sight. Identifying 416 cluster galaxies, we use kinematics to trace the radial mass profile of the halo, providing a mass estimate independent from the lens model. We also measure radially averaged properties of the cluster members, tracking their evolution as a function of infall. Thanks to the high spatial resolution of our data, we identify six cluster members acting as galaxy–galaxy lenses, which constrain localized mass distributions beyond the Einstein radius. Finally, taking advantage of MUSE’s 3D capabilities, we detect and analyse multiple spatially extended overdensities outside of the cluster that influence lensing-derived halo mass estimates. We stress that much of this work is only possible thanks to the robust, extended IFU coverage, highlighting its importance even in less optically dense cluster regions. Overall, this work showcases the power of combining HST + MUSE, and serves as the initial step towards a larger and wider program targeting several clusters

BUFFALO/Flashlights: Constraints on the abundance of lensed supergiant stars in the Spock galaxy at redshift 1

We present a constraint on the abundance of supergiant (SG) stars at redshift z approx. 1, based on recent observations of a strongly lensed arc at this redshift. First we derive a free-form model of MACS J0416.1-2403 using data from the BUFFALO program. The new lens model is based on 72 multiply lensed galaxies that produce 214 multiple images, making it the largest sample of spectroscopically confirmed lensed galaxies on this cluster. The larger coverage in BUFFALO allows us to measure the shear up to the outskirts of the cluster, and extend the range of lensing constraints up to ~ 1 Mpc from the central region, providing a mass estimate up to this radius. As an application, we make predictions for the number of high-redshift multiply-lensed galaxies detected in future observations with JWST. Then we focus on a previously known lensed galaxy at z=1.0054, nicknamed Spock, which contains four previously reported transients. We interpret these transients as microcaustic crossings of SG stars and compute the probability of such events. Based on simplifications regarding the stellar evolution, we find that microlensing (by stars in the intracluster medium) of SG stars at z=1.0054 can fully explain these events. The inferred abundance of SG stars is consistent with either (1) a number density of stars with bolometric luminosities beyond the Humphreys-Davidson (HD) limit (L ~ $6\times10^5 L_{\odot}$) that is below 400 stars per sq. kpc, or (2) the absence of stars beyond the HD limit but with a SG number density of ~ 9000 per sq. kpc for stars with luminosities between $10^5$ and $6\times10^5$. This is equivalent to one SG star per 10x10 pc$^2$. We finally make predictions for future observations with JWST's NIRcam. We find that in observations made with the F200W filter that reach 29 mag AB, if cool red SG stars exist at z~1 beyond the HD limit, they should be easily detected in this arcComment: 24 pages & 18 figure

BUFFALO/Flashlights: Constraints on the abundance of lensed supergiant stars in the Spock galaxy at redshift 1

In this work, we present a constraint on the abundance of supergiant (SG) stars at redshift z ≈ 1, based on recent observations of astrongly lensed arc at this redshift. First we derived a free-form model of MACS J0416.1-2403 using data from the Beyond Ultradeep Frontier Fields and Legacy Observations (BUFFALO) program. The new lens model is based on 72 multiply lensed galaxies thatproduce 214 multiple images, making it the largest sample of spectroscopically confirmed lensed galaxies on this cluster. The largercoverage in BUFFALO allowed us to measure the shear up to the outskirts of the cluster, and extend the range of lensing constraintsup to ∼1 Mpc from the central region, providing a mass estimate up to this radius. As an application, we make predictions for thenumber of high-redshift multiply lensed galaxies detected in future observations with the James Webb Space Telescope (JWST).Then we focus on a previously known lensed galaxy at z = 1.0054, nicknamed Spock, which contains four previously reportedtransients. We interpret these transients as microcaustic crossings of SG stars and explain how we computed the probability of suchevents. Based on simplifications regarding the stellar evolution, we find that microlensing (by stars in the intracluster medium) ofSG stars at z = 1.0054 can fully explain these events. The inferred abundance of SG stars is consistent with either (1) a numberdensity of stars with bolometric luminosities beyond the Humphreys-Davidson (HD) limit (Lmax ≈ 6 × 105 L for red stars), whichis below ∼400 stars kpc−2, or (2) the absence of stars beyond the HD limit but with a SG number density of ∼9000 kpc−2 for starswith luminosities between 105 L and 6 × 105 L. This is equivalent to one SG star per 10 × 10 pc2. Finally, we make predictions forfuture observations with JWST’s NIRcam. We find that in observations made with the F200W filter that reach 29 mag AB, if cool red SG stars exist at z ≈ 1 beyond the HD limit, they should be easily detected in this arc

CD14 Deficiency Impacts Glucose Homeostasis in Mice through Altered Adrenal Tone

The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis

Worldwide diversity of endophytic fungi and insects associated with dormant tree twigs

International trade in plants and climate change are two of the main factors causing damaging tree pests (i.e. fungi and insects) to spread into new areas. To mitigate these risks, a large-scale assessment of tree-associated fungi and insects is needed. We present records of endophytic fungi and insects in twigs of 17 angiosperm and gymnosperm genera, from 51 locations in 32 countries worldwide. Endophytic fungi were characterized by high-throughput sequencing of 352 samples from 145 tree species in 28 countries. Insects were reared from 227 samples of 109 tree species in 18 countries and sorted into taxonomic orders and feeding guilds. Herbivorous insects were grouped into morphospecies and were identified using molecular and morphological approaches. This dataset reveals the diversity of tree-associated taxa, as it contains 12,721 fungal Amplicon Sequence Variants and 208 herbivorous insect morphospecies, sampled across broad geographic and climatic gradients and for many tree species. This dataset will facilitate applied and fundamental studies on the distribution of fungal endophytes and insects in trees

Measurement of the t(t)over-bar production cross section in pp collisions at root s=7 TeV in dilepton final states containing a tau

The top quark pair production cross section is measured in dilepton events with one electron or muon, and one hadronically decaying tau lepton from the decay t (t) over bar -> (l nu(l))((sic)(h)nu((sic)))b (b) over bar, (l = e, mu). The data sample corresponds to an integrated luminosity of 2.0 fb(-1) for the electron channel and 2.2 fb(-1) for the muon channel, collected by the CMS detector at the LHC. This is the first measurement of the t (t) over bar cross section explicitly including tau leptons in proton- proton collisions at root s = 7 TeV. The measured value sigma(t (t) over bar) = 143 +/- 14(stat) +/- 22(syst) +/- 3(lumi) pb is consistent with the standard model predictions

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

A first update on mapping the human genetic architecture of COVID-19

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