Revising the structure of a new eicosanoid from human platelets to 8,9-11,12-diepoxy-13-hydroxy-eicosadienoic acid

Eicosanoids are critical mediators of fever, pain, and inflammation generated by immune and tissue cells. We recently described a new bioactive eicosanoid generated by cyclooxygenase-1 (COX-1) turnover during platelet activation that can stimulate human neutrophil integrin expression. On the basis of mass spectrometry (MS/MS and MS3), stable isotope labeling, and GC-MS analysis, we previously proposed a structure of 8-hydroxy-9,11-dioxolane eicosatetraenoic acid (DXA3). Here, we achieved enzymatic synthesis and 1H NMR characterization of this compound with results in conflict with the previously proposed structural assignment. Accordingly, by using LC-MS, we screened autoxidation reactions of 11-hydroperoxy-eicosatetraenoic acid (11-HpETE) and thereby identified a candidate sharing the precise reverse-phase chromatographic and MS characteristics of the platelet product. We optimized these methods to increase yield, allowing full structural analysis by 1H NMR. The revised assignment is presented here as 8,9–11,12-diepoxy-13-hydroxyeicosadienoic acid, abbreviated to 8,9–11,12-DiEp-13-HEDE or DiEpHEDE, substituted for the previous name DXA3. We found that in platelets, the lipid likely forms via dioxolane ring opening with rearrangement to the diepoxy moieties followed by oxygen insertion at C13. We present its enzymatic biosynthetic pathway and MS/MS fragmentation pattern and, using the synthetic compound, demonstrate that it has bioactivity. For the platelet lipid, we estimate 16 isomers based on our current knowledge (and four isomers for the synthetic lipid). Determining the exact isomeric structure of the platelet lipid remains to be undertaken

Countrywide flood forecasting in Scotland: challenges for hydrometeorological model uncertainty and prediction

The Scottish Flood Forecasting Service, a new partnership between the Met Office and the Scottish Environment Protection Agency, aims to make best use of weather and river forecasting expertise in providing improved flood resilience and vigilance for emergency responders across Scotland. Flood guidance employs a blend of experience, professional assessment and input from meteorological and hydrological models. For countrywide forecasts, the CEH-developed Grid-to-Grid model is planned to be the key forecasting tool: it employs rainfall estimates from raingauges, radar and weather models to produce forecast river flows up to 5 days ahead on a 1-km grid across the Scottish mainland. Probabilistic flood forecasts, using ensemble rainfalls as input, are planned in a future phase. Use of rainfall as input to hydrological models is a challenge in Scotland, especially given the terrain and sparse radar and raingauge network coverage, and makes forecasting uncertain. However, the merged hydrological and meteorological capabilities of the new service bring tangible benefits for improved flood forecasting

Investigation of the initiation and extent of ductile pipe rupture : quarterly progress report for ... /

Includes bibliographical references.Work performed by the Battelle Memorial InstituteMode of access: Internet.Latest issue consulted: BMI-1847 (Apr/Jun 1968).Description based on: BMI-1817 (Jul/Sep 1967); title from title page