L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome. We find that the actin-bundling protein L-plastin (LPL) significantly enhances NLRP3 assembly. Specifically, LPL enables apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) oligomerization during NLRP3 assembly by stabilizing ASC interactions with the kinase Pyk2, a component of cell-surface adhesive structures called podosomes. Upon treatment with exogenous NLRP3 activators, lung-resident alveolar macrophages (AMs) lacking LPL exhibit reduced caspase-1 activity, IL-1β cleavage, and gasdermin-D processing. LP

Global application of an unoccupied aerial vehicle photogrammetry protocol for predicting aboveground biomass in non‐forest ecosystems

P. 1-15Non-forest ecosystems, dominated by shrubs, grasses and herbaceous plants, provide ecosystem services including carbon sequestration and forage for grazing, and are highly sensitive to climatic changes. Yet these ecosystems are poorly represented in remotely sensed biomass products and are undersampled by in situ monitoring. Current global change threats emphasize the need for new tools to capture biomass change in non-forest ecosystems at appropriate scales. Here we developed and deployed a new protocol for photogrammetric height using unoccupied aerial vehicle (UAV) images to test its capability for delivering standardized measurements of biomass across a globally distributed field experiment. We assessed whether canopy height inferred from UAV photogrammetry allows the prediction of aboveground biomass (AGB) across low-stature plant species by conducting 38 photogrammetric surveys over 741 harvested plots to sample 50 species. We found mean canopy height was strongly predictive of AGB across species, with a median adjusted R2 of 0.87 (ranging from 0.46 to 0.99) and median prediction error from leave-one-out cross-validation of 3.9%. Biomass per-unit-of-height was similar within but different among, plant functional types. We found that photogrammetric reconstructions of canopy height were sensitive to wind speed but not sun elevation during surveys. We demonstrated that our photogrammetric approach produced generalizable measurements across growth forms and environmental settings and yielded accuracies as good as those obtained from in situ approaches. We demonstrate that using a standardized approach for UAV photogrammetry can deliver accurate AGB estimates across a wide range of dynamic and heterogeneous ecosystems. Many academic and land management institutions have the technical capacity to deploy these approaches over extents of 1–10 ha−1. Photogrammetric approaches could provide much-needed information required to calibrate and validate the vegetation models and satellite-derived biomass products that are essential to understand vulnerable and understudied non-forested ecosystems around the globe.S

Bypassing ubiquitination enables LAT recycling to the cell surface and enhanced signaling in T cells.

LAT molecules defective in ubiquitination have an increased half-life and induce enhanced signaling when expressed in T cells. In this study, we have examined the role of ubiquitination in regulating LAT endocytosis, recycling, and degradation in resting and stimulated T cells. By tracking and comparing plasma membrane-labeled wild type and ubiquitination-resistant 2KR LAT, we find that ubiquitination promotes the degradation of surface LAT in T cells. Activation of T cells increases LAT ubiquitination and promotes trafficking of internalized LAT to lysosomes for degradation. Ubiquitination of LAT does not change internalization rates from the cell surface, but prevents efficient recycling of LAT to the surface of T cells. Our study demonstrates that surface LAT levels are tightly controlled by ubiquitination. LAT in unstimulated cells lacks ubiquitin allowing for increased LAT stability and efficient T cell activation upon TCR triggering; ubiquitination leads to efficient removal of LAT after activation

Patterns of Marijuana Use in a 6-Month Pain Management Sample in the United States

This study is a 6-month retrospective analysis of urine drug testing (UDT) data from a pain management population among specimens with clinician-ordered marijuana testing (N = 194 809). Descriptive statistics about the specimen positivity of clinician-ordered marijuana UDT are provided as well as other drug positivity. Specimens from men and adults aged 18 to 34 years had the highest prevalence rates of marijuana positivity. The prevalence of past-month marijuana use among a comparative national population was lower than the prevalence of positive marijuana tests in the UDT specimens by all characteristics. Among the specimens tested for illicit drugs and marijuana, 4.0% were positive for amphetamine, 2.8% were positive for cocaine, and 0.9% were positive for heroin. The most common prescription drugs listed were opioids (64.7%), benzodiazepines (20.5%), and antidepressants (19.9%). In sum, the findings reflect previous research showing high rates of marijuana use, illicit drug use, and prescription drug use in a pain management population