Why Trade Associations Matter: Exploring Function, Meaning, and Influence

We explore the organizational characteristics of trade associations (TAs) and suggest theoretical approaches for undertaking research into or involving TAs in management and organization studies. Through emphasizing the role of TAs within and between industries and at the interface of business and society, we consider how TAs generate meaning and influence

TLR2 and Caspase-1 Signaling are Critical for Bacterial Containment But Not Clearance During Craniotomy-Associated Biofilm Infection

BACKGROUND: A craniotomy is required to access the brain for tumor resection or epilepsy treatment, and despite precautionary measures, infectious complications occur at a frequency of 1-3%. Approximately half of craniotomy infections are caused by Staphylococcus aureus (S. aureus) that forms a biofilm on the bone flap, which is recalcitrant to antibiotics. Our prior work in a mouse model of S. aureus craniotomy infection revealed a critical role for myeloid differentiation factor 88 (MyD88) in bacterial containment and pro-inflammatory mediator production. Since numerous receptors utilize MyD88 as a signaling adaptor, the current study examined the importance of Toll-like receptor 2 (TLR2) and TLR9 based on their ability sense S. aureus ligands, namely lipoproteins and CpG DNA motifs, respectively. We also examined the role of caspase-1 based on its known association with TLR signaling to promote IL-1β release. METHODS: A mouse model of craniotomy-associated biofilm infection was used to investigate the role of TLR2, TLR9, and caspase-1 in disease progression. Wild type (WT), TLR2 knockout (KO), TLR9 KO, and caspase-1 KO mice were examined at various intervals post-infection to quantify bacterial burden, leukocyte recruitment, and inflammatory mediator production in the galea, brain, and bone flap. In addition, the role of TLR2-dependent signaling during microglial/macrophage crosstalk with myeloid-derived suppressor cells (MDSCs) was examined. RESULTS: TLR2, but not TLR9, was important for preventing S. aureus outgrowth during craniotomy infection, as revealed by the elevated bacterial burden in the brain, galea, and bone flap of TLR2 KO mice concomitant with global reductions in pro-inflammatory mediator production compared to WT animals. Co-culture of MDSCs with microglia or macrophages, to model interactions in the brain vs. galea, respectively, also revealed a critical role for TLR2 in triggering pro-inflammatory mediator production. Similar to TLR2, caspase-1 KO animals also displayed increased S. aureus titers coincident with reduced pro-inflammatory mediator release, suggestive of pathway cooperativity. Treatment of caspase-1 KO mice with IL-1β microparticles significantly reduced S. aureus burden in the brain and galea compared to empty microparticles, confirming the critical role of IL-1β in limiting S. aureus outgrowth during craniotomy infection. CONCLUSIONS: These results demonstrate the existence of an initial anti-bacterial response that depends on both TLR2 and caspase-1 in controlling S. aureus growth; however, neither pathway is effective at clearing infection in the WT setting, since craniotomy infection persists when both molecules are present

Evryscope and K2 Constraints on TRAPPIST-1 Superflare Occurrence and Planetary Habitability

The nearby ultracool dwarf TRAPPIST-1 possesses several Earth-sized terrestrial planets, three of which have equilibrium temperatures that may support liquid surface water, making it a compelling target for exoplanet characterization. TRAPPIST-1 is an active star with frequent flaring, with implications for the habitability of its planets. Superflares (stellar flares whose energy exceeds 1033 erg) can completely destroy the atmospheres of a cool star's planets, allowing ultraviolet radiation and high-energy particles to bombard their surfaces. However, ultracool dwarfs emit little ultraviolet flux when quiescent, raising the possibility of frequent flares being necessary for prebiotic chemistry that requires ultraviolet light. We combine Evryscope and Kepler observations to characterize the high-energy flare rate of TRAPPIST-1. The Evryscope is an array of 22 small telescopes imaging the entire Southern sky in g' every two minutes. Evryscope observations, spanning 170 nights over 2 yr, complement the 80 day continuous short-cadence K2 observations by sampling TRAPPIST-1's long-term flare activity. We update TRAPPIST-1's superflare rate, finding a cumulative rate of 4.2−0.2+1.9 superflares per year. We calculate the flare rate necessary to deplete ozone in the habitable-zone planets' atmospheres, and find that TRAPPIST-1's flare rate is insufficient to deplete ozone if present on its planets. In addition, we calculate the flare rate needed to provide enough ultraviolet flux to power prebiotic chemistry. We find TRAPPIST-1's flare rate is likely insufficient to catalyze some of the Earthlike chemical pathways thought to lead to ribonucleic acid synthesis, and flux due to flares in the biologically relevant UV-B band is orders of magnitude less for any TRAPPIST-1 planet than has been experienced by Earth at any time in its history

EvryFlare. I. Long-term Evryscope Monitoring of Flares from the Cool Stars across Half the Southern Sky

We search for superflares from 4068 cool stars in 2+ yr of Evryscope photometry, focusing on those with high-cadence data from both Evryscope and the Transiting Exoplanet Survey Satellite (TESS). The Evryscope array of small telescopes observed 575 flares from 284 stars, with a median energy of 1034.0 erg. Since 2016, Evryscope has enabled the detection of rare events from all stars observed by TESS through multi-year, high-cadence continuous observing. We report around twice the previous largest number of 1034 erg high-cadence flares from nearby cool stars. We find eight flares with amplitudes of 3+ g' magnitudes, with the largest reaching 5.6 mag and releasing 1036.2 erg. We observe a 1034 erg superflare from TOI-455 (LTT 1445), a mid-M with a rocky planet candidate. We measure the superflare rate per flare-star and quantify the average flaring of active stars as a function of spectral type, including superflare rates, flare frequency distributions, and typical flare amplitudes in g'. We confirm superflare morphology is broadly consistent with magnetic reconnection. We estimate starspot coverage necessary to produce superflares, and hypothesize maximum allowed superflare energies and waiting times between flares corresponding to 100% coverage of the stellar hemisphere. We observe decreased flaring at high Galactic latitudes. We explore the effects of superflares on ozone loss to planetary atmospheres: we observe one superflare with sufficient energy to photodissociate all ozone in an Earth-like atmosphere in one event. We find 17 stars that may deplete an Earth-like atmosphere via repeated flaring. Of the 1822 stars around which TESS may discover temperate rocky planets, we observe 14.6% ± 2% emit large flares

EvryFlare. II. Rotation Periods of the Cool Flare Stars in TESS across Half the Southern Sky

We measure rotation periods and sinusoidal amplitudes in Evryscope light curves for 122 two-minute K5–M4 TESS targets selected for strong flaring. The Evryscope array of telescopes has observed all bright nearby stars in the south, producing 2-minute cadence light curves since 2016. Long-term, high-cadence observations of rotating flare stars probe the complex relationship between stellar rotation, starspots, and superflares. We detect periods from 0.3487 to 104 days and observe amplitudes from 0.008 to 0.216 g' mag. We find that the Evryscope amplitudes are larger than those in TESS with the effect correlated to stellar mass (p-value = 0.01). We compute the Rossby number (Ro) and find that our sample selected for flaring has twice as many intermediate rotators (0.04 Ro Ro Ro > 0.44) rotators; this may be astrophysical or a result of period detection sensitivity. We discover 30 fast, 59 intermediate, and 33 slow rotators. We measure a median starspot coverage of 13% of the stellar hemisphere and constrain the minimum magnetic field strength consistent with our flare energies and spot coverage to be 500 G, with later-type stars exhibiting lower values than earlier-type stars. We observe a possible change in superflare rates at intermediate periods. However, we do not conclusively confirm the increased activity of intermediate rotators seen in previous studies. We split all rotators at Ro ∼ 0.2 into bins of PRot PRot > 10 days to confirm that short-period rotators exhibit higher superflare rates, larger flare energies, and higher starspot coverage than do long-period rotators, at p-values of 3.2 × 10−5, 1.0 × 10−5, and 0.01, respectively

Staphylococcus aureus ATP Synthase Promotes Biofilm Persistence by Influencing Innate Immunity

ABSTRACT Staphylococcus aureus is a major cause of prosthetic joint infection (PJI), which is characterized by biofilm formation. S. aureus biofilm skews the host immune response toward an anti-inflammatory profile by the increased recruitment of myeloid-derived suppressor cells (MDSCs) that attenuate macrophage proinflammatory activity, leading to chronic infection. A screen of the Nebraska Transposon Mutant Library identified several hits in the ATP synthase operon that elicited a heightened inflammatory response in macrophages and MDSCs, including atpA, which encodes the alpha subunit of ATP synthase. An atpA transposon mutant (ΔatpA) had altered growth kinetics under both planktonic and biofilm conditions, along with a diffuse biofilm architecture that was permissive for leukocyte infiltration, as observed by confocal laser scanning microscopy. Coculture of MDSCs and macrophages with ΔatpA biofilm elicited significant increases in the proinflammatory cytokines interleukin 12p70 (IL-12p70), tumor necrosis factor alpha (TNF-α), and IL-6. This was attributed to increased leukocyte survival resulting from less toxin and protease production by ΔatpA biofilm as determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The enhanced inflammatory response elicited by ΔatpA biofilm was cell lysis-dependent since it was negated by polyanethole sodium sulfanate treatment or deletion of the major autolysin, Atl. In a mouse model of PJI, ΔatpA-infected mice had decreased MDSCs concomitant with increased monocyte/macrophage infiltrates and proinflammatory cytokine production, which resulted in biofilm clearance. These studies identify S. aureus ATP synthase as an important factor in influencing the immune response during biofilm-associated infection and bacterial persistence. IMPORTANCE Medical device-associated biofilm infections are a therapeutic challenge based on their antibiotic tolerance and ability to evade immune-mediated clearance. The virulence determinants responsible for bacterial biofilm to induce a maladaptive immune response remain largely unknown. This study identified a critical role for S. aureus ATP synthase in influencing the host immune response to biofilm infection. An S. aureus ATP synthase alpha subunit mutant (ΔatpA) elicited heightened proinflammatory cytokine production by leukocytes in vitro and in vivo, which coincided with improved biofilm clearance in a mouse model of prosthetic joint infection. The ability of S. aureus ΔatpA to augment host proinflammatory responses was cell lysis-dependent, as inhibition of bacterial lysis by polyanethole sodium sulfanate or a ΔatpAΔatl biofilm did not elicit heightened cytokine production. These studies reveal a critical role for AtpA in shaping the host immune response to S. aureus biofilm

Variables in the Southern Polar Region Evryscope 2016 Data Set

The regions around the celestial poles offer the ability to find and characterize long-term variables from ground-based observatories. We used multi-year Evryscope data to search for high-amplitude (≈5% or greater) variable objects among 160,000 bright stars (mv σ limiting magnitude of g = 16 in dark time. In this study, covering all stars 9 M⊙) secondaries with K-dwarf primaries, strong candidates for precision mass–radius measurements

EvryFlare. III. Temperature Evolution and Habitability Impacts of Dozens of Superflares Observed Simultaneously by Evryscope and TESS

Superflares may provide the dominant source of biologically relevant UV radiation to rocky habitable-zone M-dwarf planets (M-Earths), altering planetary atmospheres and conditions for surface life. The combined line and continuum flare emission has usually been approximated by a 9000 K blackbody. If superflares are hotter, then the UV emission may be 10 times higher than predicted from the optical. However, it is unknown for how long M-dwarf superflares reach temperatures above 9000 K. Only a handful of M-dwarf superflares have been recorded with multiwavelength high-cadence observations. We double the total number of events in the literature using simultaneous Evryscope and Transiting Exoplanet Survey Satellite observations to provide the first systematic exploration of the temperature evolution of M-dwarf superflares. We also increase the number of superflaring M dwarfs with published time-resolved blackbody evolution by ∼10×. We measure temperatures at 2 minutes cadence for 42 superflares from 27 K5–M5 dwarfs. We find superflare peak temperatures (defined as the mean of temperatures corresponding to flare FWHM) increase with flare energy and impulse. We find the amount of time flares emit at temperatures above 14,000 K depends on energy. We discover that 43% of the flares emit above 14,000 K, 23% emit above 20,000 K and 5% emit above 30,000 K. The largest and hottest flare briefly reached 42,000 K. Some do not reach 14,000 K. During superflares, we estimate M-Earths orbiting <200 Myr stars typically receive a top-of-atmosphere UV-C flux of ∼120 W m−2 and up to 103 W m−2, 100–1000 times the time-averaged X-ray and UV flux from Proxima Cen

Analysis of Qa-1bPeptide Binding Specificity and the Capacity of Cd94/Nkg2a to Discriminate between Qa-1–Peptide Complexes

The major histocompatibility complex class Ib protein, Qa-1b, serves as a ligand for murine CD94/NKG2A natural killer (NK) cell inhibitory receptors. The Qa-1b peptide-binding site is predominantly occupied by a single nonameric peptide, Qa-1 determinant modifier (Qdm), derived from the leader sequence of H-2D and L molecules. Five anchor residues were identified in this study by measuring the peptide-binding affinities of substituted Qdm peptides in experiments with purified recombinant Qa-1b. A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions. The results indicate that Qa-1b can bind a diverse repertoire of peptides but that Qdm has an optimal primary structure for binding Qa-1b. Flow cytometry experiments with Qa-1b tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1b complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. Our findings suggest that it may be difficult for viruses to generate decoy peptides that mimic Qdm and raise the possibility that competitive replacement of Qdm with other peptides may provide a novel mechanism for activation of NK cells

MyD88 expression by CNS-resident cells is pivotal for eliciting protective immunity in brain abscesses

MyD88 KO (knockout) mice are exquisitely sensitive to CNS (central nervous system) infection with Staphylococcus aureus, a common aetiological agent of brain abscess, exhibiting global defects in innate immunity and exacerbated tissue damage. However, since brain abscesses are typified by the involvement of both activated CNS-resident and infiltrating immune cells, in our previous studies it has been impossible to determine the relative contribution of MyD88-dependent signalling in the CNS compared with the peripheral immune cell compartments. In the present study we addressed this by examining the course of S. aureus infection in MyD88 bone marrow chimaera mice. Interestingly, chimaeras where MyD88 was present in the CNS, but not bone marrow-derived cells, mounted pro-inflammatory mediator expression profiles and neutrophil recruitment equivalent to or exceeding that detected in WT (wild-type) mice. These results implicate CNS MyD88 as essential in eliciting the initial wave of inflammation during the acute response to parenchymal infection. Microarray analysis of infected MyD88 KO compared with WT mice revealed a preponderance of differentially regulated genes involved in apoptotic pathways, suggesting that the extensive tissue damage characteristic of brain abscesses from MyD88 KO mice could result from dysregulated apoptosis. Collectively, the findings of the present study highlight a novel mechanism for CNS-resident cells in initiating a protective innate immune response in the infected brain and, in the absence of MyD88 in this compartment, immunity is compromised