Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury

Smoke inhalation associated with structural fires, wildfires, or explosions leads to lung injury, for which innovative and clinically relevant animal models are needed to develop effective therapeutics. We have previously reported that damage-associated molecular patterns (DAMPs) and anti-inflammatory cytokines correlate with infectious complications in patients diagnosed with inhalational injury. In this study, we describe a novel and translational murine model of acute inhalational injury characterized by an accumulation of protein and neutrophils in the bronchoalveolar space, as well as histological evidence of tissue damage. Mice were anesthetized, and a cannula was placed in the trachea and exposed to smoldering plywood smoke three times for 2-min intervals in a smoke chamber. Here we demonstrate that this model recapitulates clinically relevant phenotypes, including early release of double-stranded DNA (dsDNA), IL-10, monocyte chemoattractant protein (MCP)-1, and CXCL1 along with neutrophilia early after injury, accompanied by subsequent susceptibility to opportunistic infection with Pseudomonas aeruginosa. Further investigation of the model, and in turn a reanalysis of patient samples, revealed a late release of the DAMP hyaluronic acid (HA) from the lung. Using nitric oxide synthase-deficient mice, we found that Nos2 was required for increases in IL-10, MCP-1, and HA following injury but not release of dsDNA, CXCL1 expression, early neutrophilia, or susceptibility to opportunistic infection. Depletion of CXCL1 attenuated early neutrophil recruitment, leading to decreased histopathology scores and improved bacterial clearance in this model of smoke inhalation. Together, these data highlight the potential therapeutic benefit of attenuating neutrophil recruitment in the first 24 h after injury in patients

Phylogenomic analysis of a 55.1 kb 19-gene dataset resolves a monophyletic Fusarium that includes the Fusarium solani Species Complex

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user¿s needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option availabl

Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at $\sqrt{s} = 900$ GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region $(|\eta|<0.8)$ over the transverse momentum range $0.15<p_{\rm T}<10$ GeV/$c$. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for $|\eta|<0.8$ is $\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001$ (stat.) $\pm0.007$ (syst.) GeV/$c$ and \left_{\rm NSD}=0.489\pm0.001 (stat.) $\pm0.007$ (syst.) GeV/$c$, respectively. The data exhibit a slightly larger $\left<p_{\rm T}\right>$ than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390

The structure and evolution of the Lagoon Nebula. I. Submillimeter continuum and CO line mapping

We present submillimeter- and millimeter-wave maps tracing the molecular gas and dust around the edge of the H II region M8. The molecular material is clumped into cores on the scale of the beam (about 0.1 pc) whose temperatures can be estimated from CO observations. The masses of the clumps, estimated from their continuum fluxes, are consistent with a power-law mass function with index -1.7 +/- 0.6, which agrees with determinations for other molecular clouds at similar resolutions, using molecular lines as tracers. The submillimeter clumps are sited at the interface between the H II region and the background molecular cloud, where they are exposed to the ultraviolet flux of OB stars. The physical parameters of the clumps are compared to published models of molecular clouds undergoing photoevaporation, suggesting that the pressure of the ionized gas exceeds the internal pressure of the clumps and, therefore, that a shock front will be driven into the clumps. The clumps themselves currently appear to be gravitationally unbound, but the compression may be sufficient to induce collapse