Resolution of acute inflammation is an active process coordinated by proresolving lipid mediators (SPMs) such as lipoxins (LXs) and resolvins (Rvs), which are formed by the concerted action of 2 lipoxygenases (LOs). Because the exact molecular mechanisms of SPM biosynthesis are not completely understood, we aimed to investigate LX and D-type Rv formation in human leukocytes and HEK293T cells overexpressing leukotriene (LT) pathway enzymes. Activity assays in precursor (15-hydroxyeicosatetraenoic acids, 17-HDoHE)-treated granulocytes [polymorphonuclear leukocytes (PMNLs)] showed a strict dependence of LXA 4 /RvD 1 biosynthesis on cell integrity, and incubation with recombinant human 5-LO did not lead to LX or Rv formation. Pharmacologic inhibition of 5-LO activating protein (FLAP) by MK-886 inhibited LXA 4 /RvD 1 biosynthesis in precursor-treated PMNLs (drug concentration causing 50% inhibition ∼0.3/0.2 mM), as did knockdown of the enzyme in MM6 cells, and precursor-treated HEK293T overexpressing 5-LO produced high amounts of LXA 4 only in the presence of FLAP. In addition, inhibition of cytosolic phospholipase A 2a (cPLA 2a ) interfered with LXA 4 / RvD 1 formation from exogenous precursors in PMNLs. Furthermore, inhibition of the LT synthases LTA 4 hydrolase and LTC 4 synthase in PMNL/platelet coincubations augmented LXA 4 levels. These findings show that several enzymes known to be involved in the biosynthesis of proinflammatory LTs, such as FLAP and cPLA 2a , also contribute to LX and Rv formation.-

Eurasian buzzards which have liver concentrations likely to be associated with lethal and sublethal effects is probably obtained when they prey upon or scavenge gamebirds and mammals shot using Pb shotgun pellets.

No abstract

Recent wildfire activity in semi-arid regions like western North America exceeds the range of historical records. High-resolution paleoclimate archives such as stalagmites could illuminate the link between hydroclimate, vegetation change, and fire activity in pre-anthropogenic climate states beyond the timescale of existing tree-ring records. Here we present an analysis of levoglucosan, a combustion-sensitive anhydrosugar, and lignin oxidation products (LOPs) in a stalagmite, reconstructing fire activity and vegetation composition in the California Coast Range across the 8.2 kyr event. Elevated levoglucosan concentrations suggest increased fire activity while altered LOP compositions indicate a shift toward more woody vegetation during the event. These changes are concurrent with increased hydroclimate volatility as shown by carbon and calcium isotope proxies. Together, these records suggest that climate whiplash (oscillations between extreme wetness and aridity) and fire activity in California, both projected to increase with anthropogenic climate change, were tightly coupled during the early Holocene.

The activation and infiltration of polymorphonuclear neutrophils (PMN) are critical key steps in inflammation. PMN-mediated inflammation is limited by anti-inflammatory and pro-resolving mechanisms, including specialized pro-resolving lipid mediators (SPM). We examined the effects of 15-epi-LXA4 on inflammation and the biosynthesis of pro-inflammatory mediators, such as prostaglandins, leukotriene B4 and various hydroxyeicosatetraenoic acids and SPM, in an oxazolone (OXA)-induced hypersensitivity model for dermal inflammation. 15-epi-LXA4 (100 μM, 5 μL subcutaneously injected) significantly (P < 0.05) reduced inflammation in skin, 24 hours after the OXA challenge, as compared to skin treated with vehicle. No significant influence on the biosynthesis of prostaglandins or leukotriene B4 was observed, whereas the level of 15S-hydroxy-eicosatetraenoic acid was significantly (P < 0.05) lower in the skin areas treated with 15-epi-LXA4. In spite of the use of a fully validated analytical procedure, no SPM were detected in the biological samples. To investigate the reason for the lack of analytical signal, we tried to mimic the production of SPM (lipoxins, resolvins, maresin and protectin) by injecting them subcutaneously into the skin of mice and studying the in vivo availability and distribution of the compounds. All analytes showed very little lateral distribution in skin tissue and their levels were markedly decreased (> 95%) 2 hours after injection. However, docosahexaenoic acid derivatives were biologically more stable than SPM derived from arachidonic acid or eicosapentaenoic acid.