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The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.
Native vegetation of the upper Murrumbidgee catchment in southeast NSW and the Australian Capital-Territory (ACT) was classified into 75 plant communities across 18 NSW Vegetation Classes within nine Structural-Formations. Plant communities were derived through numerical analysis of 4,106 field survey plots including 3,787-plots from 58 existing survey datasets and 319 new plots, which were sampled in under surveyed ecosystems. All plant-communities are described at a level appropriate for discrimination of threatened ecological communities and distinct-vegetation mapping units.
The classification describes plant communities in the context of the upper Murrumbidgee catchment and surrounding-landscapes of similar ecological character. It incorporates and, in some instances, refines identification of plant-communities described in previous classifications of alpine vegetation, forest ecosystems, woodlands and grasslands-across the Australian Alps and South Eastern Highlands within the upper Murrumbidgee catchment. Altitude,-precipitation, soil saturation, lithology, slope, aspect and landscape position were all important factors in guiding-plant community associations.
Nine Threatened Ecological Communities under Commonwealth, NSW and ACT legislation occur in the upper-Murrumbidgee catchment. This study has also identified five additional plant communities which are highly restricted-in distribution and may require active management or protection to ensure their survival.