Restoration has been elevated as an important strategy to reverse the decline of coastal wetlands worldwide. Current practice in restoration science emphasizes minimizing competition between ...outplanted propagules to maximize planting success. This paradigm persists despite the fact that foundational theory in ecology demonstrates that positive species interactions are key to organism success under high physical stress, such as recolonization of bare substrate. As evidence of how entrenched this restoration paradigm is, our survey of 25 restoration organizations in 14 states in the United States revealed that >95% of these agencies assume minimizing negative interactions (i.e., competition) between outplants will maximize propagule growth. Restoration experiments in both Western and Eastern Atlantic salt marshes demonstrate, however, that a simple change in planting configuration (placing propagules next to, rather than at a distance from, each other) results in harnessing facilitation and increased yields by 107% on average. Thus, small adjustments in restoration design may catalyze untapped positive species interactions, resulting in significantly higher restoration success with no added cost. As positive interactions between organisms commonly occur in coastal ecosystems (especially in more physically stressful areas like uncolonized substrate) and conservation resources are limited, transformation of the coastal restoration paradigm to incorporate facilitation theory may enhance conservation efforts, shoreline defense, and provisioning of ecosystem services such as fisheries production.
Neutrophils are the most prevalent immune cells in circulation, but the repertoire of canonical inflammasomes in neutrophils and their respective involvement in neutrophil IL‐1β secretion and ...neutrophil cell death remain unclear. Here, we show that neutrophil‐targeted expression of the disease‐associated gain‐of‐function Nlrp3A350V mutant suffices for systemic autoinflammatory disease and tissue pathology in vivo. We confirm the activity of the canonical NLRP3 and NLRC4 inflammasomes in neutrophils, and further show that the NLRP1b, Pyrin and AIM2 inflammasomes also promote maturation and secretion of interleukin (IL)‐1β in cultured bone marrow neutrophils. Notably, all tested canonical inflammasomes promote GSDMD cleavage in neutrophils, and canonical inflammasome‐induced pyroptosis and secretion of mature IL‐1β are blunted in GSDMD‐knockout neutrophils. In contrast, GSDMD is dispensable for PMA‐induced NETosis. We also show that Salmonella Typhimurium‐induced pyroptosis is markedly increased in Nox2/Gp91Phox‐deficient neutrophils that lack NADPH oxidase activity and are defective in PMA‐induced NETosis. In conclusion, we establish the canonical inflammasome repertoire in neutrophils and identify differential roles for GSDMD and the NADPH complex in canonical inflammasome‐induced neutrophil pyroptosis and mitogen‐induced NETosis, respectively.
Synopsis
Canonical inflammasomes in neutrophils promote caspase‐1‐dependent cleavage of proIL‐1β and GSDMD. GSDMD mediates secretion of IL‐1β and canonical inflammasome‐induced neutrophil pyroptosis, whereas GSDMD is dispensable for NETosis induction by the phorbol ester PMA.
CAPS mutant NLRP3 in neutrophils drives autoinflammatory pathology in mice.
NLRP1b, NLRP3, NLRC4, AIM2 and Pyrin inflammasomes promote caspase‐1‐mediated pyroptosis and IL‐1β secretion in neutrophils.
Caspase‐1‐dependent cleavage of GSDMD mediates neutrophil pyroptosis and secretion of IL‐1β and DAMPs.
GSDMD is dispensable for PMA‐induced NETosis.
Canonical inflammasomes in neutrophils promote caspase‐1‐dependent cleavage of proIL‐1β and GSDMD. GSDMD mediates the secretion of IL‐1β and canonical inflammasome‐induced neutrophil pyroptosis, whereas GSDMD is dispensable for NETosis induction by the phorbol ester PMA.
Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in ...situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of ‘malignant mesothelioma, cannot exclude MMIS’ or ‘atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS’ could be used on cytology samples, adding ‘no evidence of invasion in sample provided’ for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS.
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