NLRP3 is a cytosolic pattern recognition receptor that senses microbes and endogenous danger signals. Upon activation, NLRP3 forms an inflammasome with the adapter ASC, resulting in caspase-1 ...activation, release of proinflammatory cytokines and cell death. How NLRP3 activation is regulated by transcriptional and posttranslational mechanisms to prevent aberrant activation remains incompletely understood. Here, we identify three conserved phosphorylation sites in NLRP3 and demonstrate that NLRP3 activation is controlled by phosphorylation of its pyrin domain (PYD). Phosphomimetic residues in NLRP3 PYD abrogate inflammasome activation and structural modeling indicates that phosphorylation of the PYD regulates charge-charge interaction between two PYDs that are essential for NLRP3 activation. Phosphatase 2A (PP2A) inhibition or knock-down drastically reduces NLRP3 activation, showing that PP2A can license inflammasome assembly via dephosphorylating NLRP3 PYD. These results propose that the balance between kinases and phosphatases acting on the NLRP3 PYD is critical for NLRP3 activation.
Abstract
The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5
μ
m. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and ...spectroscopy at resolutions of
λ
/Δ
λ
∼ 100–3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI.
This research investigates the potential application of generative language models, especially ChatGPT, in aviation safety analysis as a means to enhance the efficiency of safety analyses and ...accelerate the time it takes to process incident reports. In particular, ChatGPT was leveraged to generate incident synopses from narratives, which were subsequently compared with ground-truth synopses from the Aviation Safety Reporting System (ASRS) dataset. The comparison was facilitated by using embeddings from Large Language Models (LLMs), with aeroBERT demonstrating the highest similarity due to its aerospace-specific fine-tuning. A positive correlation was observed between the synopsis length and its cosine similarity. In a subsequent phase, human factors issues involved in incidents, as identified by ChatGPT, were compared to human factors issues identified by safety analysts. The precision was found to be 0.61, with ChatGPT demonstrating a cautious approach toward attributing human factors issues. Finally, the model was utilized to execute an evaluation of accountability. As no dedicated ground-truth column existed for this task, a manual evaluation was conducted to compare the quality of outputs provided by ChatGPT to the ground truths provided by safety analysts. This study discusses the advantages and pitfalls of generative language models in the context of aviation safety analysis and proposes a human-in-the-loop system to ensure responsible and effective utilization of such models, leading to continuous improvement and fostering a collaborative approach in the aviation safety domain.
Little is known about the impact of aerial 1080 control on nesting success and abundance of birds. The South Island (SI) robin (Petroica australis) is vulnerable to predation by exotic mammals, with ...declining populations on the east coast of the South Island of New Zealand. We document the effect of an aerial 1080 operation carried out in 2011 on the relative abundance of brushtail possums (Trichosurus vulpecula), rats (Rattus spp.), house mice (Mus musculus), and on SI robin nest success, comparing a site receiving aerial 1080 (Silver Peaks) to a non-treated site (Silverstream) in the Dunedin region. Although control reduced predator numbers, the relative abundance of house mice had recovered to pre-control levels after five months, as had rats after 12 months and brushtail possums after 15 months. There were no significant differences in SI robin nest success and nest survival over time between the treated and untreated sites, although negative relationships between nesting success and possum and rat abundance were observed.
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