Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein

Leukotrienes are proinflammatory products of arachidonic acid oxidation by 5-lipoxygenase that have been shown to be involved in respiratory and cardiovascular diseases. The integral membrane protein FLAP is essential for leukotriene biosynthesis. We describe the x-ray crystal structures of human FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0 and 4.2 angstrom resolution, respectively. The structures show that inhibitors bind in membrane-embedded pockets of FLAP, which suggests how these inhibitors prevent arachidonic acid from binding to FLAP and subsequently being transferred to 5-lipoxygenase, thereby preventing leukotriene biosynthesis. This structural information provides a platform for the development of therapeutics for respiratory and cardiovascular diseases.     

Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site

ObjectiveTo describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.Study designRandomized crossover experiment; prospective study.AnimalsEleven healthy adult horses between 6 and 20 years of age and weighing 487–592 kg.MethodsIn the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg^?1) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg^?1 SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.ResultsFollowing IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg^?1 minute^?1 and volume of distribution at steady-state was 3.16 ± 0.65 L kg^?1. Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.Conclusions and clinical relevanceBuprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.     

Organic acid concentrations in soil solution: effects of young coniferous trees and ectomycorrhizal fungi

Organic acids may play a key role in rhizosphere and pedogenic processes. The effects of young trees and ectomycorrhizas on the soil solution concentrations of low molecular weight organic acids (LMWOAs) were studied in soil columns (E horizon) in the presence or absence of Pinus sylvestris and Picea abies with or without three ectomycorrhizal fungi. Several LMWOAs were identified at concentrations ranging from <0.1 to 11 μM. Compared to soil columns without tree seedlings, the presence of non-mycorrhizal or mycorrhizal tree seedlings sometimes resulted in small but statistically significant increases in citrate, formate, malonate and oxalate concentration. The general nutrient concentration and low P had little short-term effect on soil solution organic acid concentrations. The results suggest that biodegradation rather than production may be the major factor regulating soil solution organic acid concentrations.     

Performance of a short tool to assess dietary intakes of fruits and vegetables, percentage energy from fat and fibre

OBJECTIVES: We describe the methods used to develop and score a 17-item 'screener' designed to estimate intake of fruit and vegetables, percentage energy from fat and fibre. The ability of this screener and a food-frequency questionnaire (FFQ) to measure these exposures is evaluated. DESIGN: Using US national food consumption data, stepwise multiple regression was used to identify the foods to be included on the instrument; multiple regression analysis was used to develop scoring algorithms. The performance of the screener was evaluated in three different studies. Estimates of intakes measured by the screener and the FFQ were compared with true usual intake based on a measurement error model. SETTING: US adult population. SUBJECTS: For development of instrument, n=9323 adults. For testing of instrument, adult men and women in three studies completing multiple 24-hour dietary recalls, FFQ and screeners, n=484, 462 and 416, respectively. RESULTS: Median recalled intakes for examined exposures were generally estimated closely by the screener. In the various validation studies, the correlations between screener estimates and estimated true intake were 0.5-0.8. In general, the performances of the screener and the full FFQ were similar; estimates of attenuation were lower for screeners than for full FFQs. CONCLUSIONS: When coupled with appropriate reference data, the screener approach described may yield useful estimates of intake, for both surveillance and epidemiological purposes.     

Costs and benefits of wild goose conservation in Scotland

This paper applies the cost-benefit analysis framework to the issue of wild geese conservation in Scotland. Wild goose numbers have risen rapidly over the past 30 years, bringing nature conservationists into conflict with farmers whose crops are damaged. We estimate the costs of damage due to goose grazing to farmers in two goose areas, Strathbeg and Islay. Conservation benefits are estimated using a contingent valuation survey of the Scottish population, and we find that benefits outweigh costs by a very considerable margin. This can be seen as providing support for recent UK government moves to compensate farmers in goose areas in order to further conservation.     

Nutritional value of a highly digestible sorghum cultivar for meat-type chickens

The nutritional value of a newly discovered sorghum mutant cultivar (P851171), with high in vitro protein digestibility, was compared to those of corn and two normal sorghums (P721N and 611Y) in two chick feeding trials. Although 8-20 day protein efficiency ratios and net protein ratios of all three sorghums were inferior to those of corn, P851171 and 611Y had markedly greater mean true amino acid digestibilities (TAAD) than either corn or P721N. In a subsequent 42-day experiment, all three sorghums supported weight gains equal to those of the corn-fed chicks. Feeding suboptimal levels of dietary protein resulted in reduced weight gains and no observed benefits of P851171 or 611Y. Furthermore, chicks fed P851171 exhibited poorer feed/gain values as compared to those fed the other cereals. It is possible that the starch content/carbohydrate profile of P851171 was inferior to that of the other sorghums, which offset its superior TAAD and resulted in poorer broiler performance.     

Plant and animal species composition and heavy metal content in fly ash ecosystems

Plant and animal species present on a coal fly ash slurry pond site and a dry deposit site were surveyed and sampled during a two-day period in October. Elemental analyses were determined for most of the species encountered. A total of 48 plant species were observed on the two sites, with 35 species on the wet site, and 20 on the dry site. Eighteen terrestrial and 7 aquatic animal species were found on the wet site, exclusive of vertebrates which were not studied with the exception of a carp (Cyprinus carpio). Eleven terrestrial invertebrates and one aquatic species were observed on the dry site. Neutron activation analysis was carried out for: Se, Hg, Cr, Ni, Zn, Co, Sb, Cd, and As. Using literature values for phytotoxicity, we conclude that, in general, plants did not accumulate toxic levels of metals. Only one plant (Impatiens biflora Willd.) showed a significant level of Cd. Of 20 plants analyzed on the wet site, 10 had excessive Se concentrations (>5 ppm); on the dry site 6 out of 18 had high Se values. In animals (Gryllus sp.; Melanoplus sp.; Trachelipus sp.; Lumbricus terrestris; Physa integra; Cyprinus carpio) the trace metal concentration was generally in between that of control animals and that of the fly ash itself. One exception included Zn, which, although the most variable element examined, was concentrated in all the terrestrial animals to levels higher than in fly ash. Crickets are the most consistent bioconcentrators with Cr, Se, and Zn at higher levels than for control animals. All animal species studied accumulated Se compared to controls.     

Mycorrhizal colonization and lead distribution in root tissues of Norway spruce seedlings

Non-inoculated spruce seedlings (Picea abies Karst.) and spruce seedlings colonized with Lactarius rufus Fr., Pisolithus tinctorius Coker & Couch or Paxillus involutus Fr. were grown for 35 or 37 weeks in a microcosm system on two types of natural forest humus differing in Pb content. Using X-ray microanalysis, the distribution and content of Pb in the tissues of mycorrhizal and non-mycorrhizal root tips were compared. No significant difference in the Pb contents of root cortex cell walls of non-mycorrhizal and seedlings colonized by Lactarius rufus, Pisolithus tinctorius, or indigenous mycorrhizal fungi (mainly Tylospora sp.) was found. However, in root tips of seedlings colonized by Paxillus involutus, due to a higher binding capacity for cations, the Pb content in cell walls of the root cortex were higher than in non-mycorrhizal roots. Pb contents in cell walls of the cortex of mycorrhizal and non-mycorrhizal roots were 3 times higher in plants growing in humus with a high Pb content than in plants growing in humus with a low Pb content. It is concluded that increasing contents of Pb in the organic matter may lead to an increased loading of the apoplast with Pb. The mycobionts tested in this investigation did not exclude Pb from root tissues.     

Selenium Removal from Irrigation Drainage Water Flowing Through Constructed Wetland Cells with Special Attention to Accumulation in Sediments

A flow-through experimental wetland system has been under investigation since 1996 to remove selenium (Se) fromagricultural drainage water in the Tulare Lake Drainage Districtat Corcoran, California, U.S.A. The system consists of ten cellswhich have dimensions of 15 × 76 m continuously flooded andvarious substrates planted. The objectives of this article are topresent the overall performance in Se removal after establishingthe wetland for three years, and to examine factors affecting Seremoval with special attention to accumulation in the sediments.In 1999, The wetland cells reduced Se from inflow water by 32 to65% in concentration and 43 to 89% in mass. Vegetationplays an important role in Se removal as non-vegetated cellshowed the least removal of Se. The inflow drainage water wasdominated by selenate (Se(VI), 91%) with smaller percentages ofselenite (Se(IV), 7%) and organic Se (org-Se(II-), 2%). Theoutflow water from the cells contained an average of 47% Se(VI),32% Se(IV) and 21% org-Se indicating reduction processesoccurring in the wetland cells. The surface sediment appears as alarge sink of Se removal. The highest Se concentration was foundin fallen litter, followed by the fine organic detrital layer onthe sediment surface. The sediment Se concentration dramaticallydecreased with increasing sediment depth. The mass distribution of Se, however, was sediment (0-20 cm) > fine detrital matter >fallen litter. Fractionation of surface sediment (0-5 cm) reveals that elemental Se was the largest fraction (ave. 47%) followedby organic matter-associated Se (34%). Soluble, adsorbed, and carbonate-associated Se accounted for 1.2, 3.1 and 2.5% ofthe total sediment Se, respectively. The major Se sink mechanism in the cells is the reduction of selenate to elemental Se andimmobilization into the organic phase of the sediments.     

Specificity of codling moth (Lepidoptera: Tortricidae) for the host plant kairomone, ethyl (2E,4Z)-2,4-decadienoate: field bioassays with pome fruit volatiles, analogue, and isomeric compounds

Codling moth, Cydia pomonella (L.), is a severe pest of apples, pears, and walnuts worldwide, and new approaches for precise monitoring and management would be beneficial. Ninety-two pome fruit volatiles were formulated in 23 distinct blends, of which a single 4-component blend of 10-carbon esters showed the only significant attraction of moths in field bioassays conducted in both walnut and apple orchards. A single constituent of this blend, ethyl (2E,4Z)-2,4-decadienoate--the "pear ester", was the major contributing attractant. The pear ester attracted both male and female moths in combined numbers that were comparable to the attractiveness of conspecific sex pheromone. Structure-activity tests were conducted in a series of orchard trials to determine the specificity of attraction of codling moths to the pear ester kairomone. No analogue 10-carbon alcohols, aldehydes, acetates, or other esters elicited significant moth capture responses. Tests with various analogue esters with alcohol chain length moiety substitutions of the (2E,4Z)-2,4-decadienoic acid elicited differential capture responses, with the ethyl exceeding the propyl, methyl, butyl, and hexyl analogues. The (E,Z) geometric isomers of this series of (2E,4Z)-2,4-decadienoic acid esters far exceeded the attractiveness of the (E,E) isomers. The pear ester is a potent attractant of both males and females, and codling moths are highly discriminating and specific in their structure-activity-based attraction to this pear-derived kairomone. These specificity attributes should allow this host plant kairomone to contribute to new abilities for female monitoring and the potential of development of novel and highly selective control practices that should decrease the current dependence on the use of broad-spectrum insecticides.