Preferential Transfer of 2-Docosahexaenoyl-1-Lysophosphatidylcholine Through an In Vitro Blood-Brain Barrier Over Unesterified Docosahexaenoic Acid

Abstract : The passage of either unesterified docosahexaenoic acid (DHA) or lysophosphatidylcholine-containing DHA (lysoPC-DHA) through an in vitro model of the blood-brain barrier was investigated. The model was constituted by a brain capillary endothelial cell monolayer set over the medium of an astrocyte culture. Cells were incubated for 4 h with a medium devoid of serum, then the endothelial cell medium was replaced by the same medium containing labeled DHA or lysoPC-DHA and incubations were performed for 2 h. DHA uptake by cells and its transfer to the lower medium (astrocyte medium when they were present) were measured. When the lower medium from preincubation and astrocytes were maintained during incubation, the passage of lysoPC-DHA was higher than that of unesterified DHA. The passage of both forms decreased when astrocytes were removed. The preference for lysoPC-DHA was not seen when the lower medium from preincubation was replaced by fresh medium, and was reversed when albumin was added to the lower medium. A preferential lysoPC-DHA passage also occurred after 2 h with brain endothelial cells cultured without astrocytes but not with aortic endothelial cells cultured and incubated under the same conditions. Altogether, these results suggest that the blood-brain barrier cells released components favoring the DHA transfer and exhibit a preference for lysoPC-DHA.     

Nance-Horan syndrome: linkage analysis in 4 families refines localization in Xp22.31–p22.13 region

Nance-Horan syndrome (NHS) is an X-linked disease characterized by severe congenital cataract with microcornea, distinctive dental findings, evocative facial features and mental impairment in some cases. Previous linkage studies have placed the NHS gene in a large region from DXS143 (Xp22.31) to DXS451 (Xp22.13). To refine this localization further, we have performed linkage analysis in four families. As the maximum expected Lod score is reached in each family for several markers in the Xp22.31–p22.13 region and linkage to the rest of the X chromosome can be excluded, our study shows that NHS is a genetically homogeneous condition. An overall maximum two-point Lod score of 9.36 (θ = 0.00) is obtained with two closely linked markers taken together, DXS207 and DXS1053 in Xp22.2. Recombinant haplotypes indicate that the NHS gene lies between DXS85 and DXS1226. Multipoint analysis yields a maximum Lod score of 9.45 with the support interval spanning a 15-cM region that includes DXS16 and DXS1229/365. The deletion map of the Xp22.3–Xp21.3 region suggests that the phenotypic variability of NHS is not related to gross rearrangement of sequences of varying size but rather to allelic mutations in a single gene, presumably located proximal to DXS16 and distal to DXS1226. Comparison with the map position of the mouse Xcat mutation supports the location of the NHS gene between the GRPR and PDHA1 genes in Xp22.2. Received: 14 June 1996 / Revised: 10 October 1996     

The response of soil solution chemistry in European forests to decreasing acid deposition

Acid deposition arising from sulphur (S) and nitrogen (N) emissions from fossil fuel combustion and agriculture has contributed to the acidification of terrestrial ecosystems in many regions globally. However, in Europe and North America, S deposition has greatly decreased in recent decades due to emissions controls. In this study, we assessed the response of soil solution chemistry in mineral horizons of European forests to these changes. Trends in pH, acid neutralizing capacity (ANC), major ions, total aluminium (Al_tot) and dissolved organic carbon were determined for the period 1995–2012. Plots with at least 10 years of observations from the ICP Forests monitoring network were used. Trends were assessed for the upper mineral soil (10–20 cm, 104 plots) and subsoil (40–80 cm, 162 plots). There was a large decrease in the concentration of sulphate () in soil solution; over a 10‐year period (2000–2010), decreased by 52% at 10–20 cm and 40% at 40–80 cm. Nitrate was unchanged at 10–20 cm but decreased at 40–80 cm. The decrease in acid anions was accompanied by a large and significant decrease in the concentration of the nutrient base cations: calcium, magnesium and potassium (Bc = Ca²⁺ + Mg²⁺ + K⁺) and Al_tot over the entire dataset. The response of soil solution acidity was nonuniform. At 10–20 cm, ANC increased in acid‐sensitive soils (base saturation ≤10%) indicating a recovery, but ANC decreased in soils with base saturation >10%. At 40–80 cm, ANC remained unchanged in acid‐sensitive soils (base saturation ≤20%,  ≤ 4.5) and decreased in better‐buffered soils (base saturation >20%,  > 4.5). In addition, the molar ratio of Bc to Al_tot either did not change or decreased. The results suggest a long‐time lag between emission abatement and changes in soil solution acidity and underline the importance of long‐term monitoring in evaluating ecosystem response to decreases in deposition.     

Food supplementation to optimize inoculative release of the predatory bug Macrolophus pygmaeus in sweet pepper

Biological control is widespread in management of greenhouse sweet pepper crops. Several species of predatory mites, bugs, and parasitoids are used against a wide range of pest species. However, biological control of particular pests like aphids, caterpillars, and the tobacco whitefly, Bemisia tabaci Gennadius, remains problematic. Macrolophus pygmaeus Rambur (Hemiptera: Miridae) is a generalist predatory bug which is used on a large scale in Western European tomato greenhouses. It has already been demonstrated that M. pygmaeus is a valuable biocontrol option in sweet pepper crops, but it has yet to find its way into common practice. Macrolophus pygmaeus should be introduced at the start of the growing season and determining an optimal release strategy is a key step in this process. In tomato crops, M. pygmaeus requires supplemental food releases to reach sufficient population numbers and dispersal levels. In this study, the need for food supplementation in sweet pepper is investigated. Three strategies were tested: (1) no food supplementation, (2) local food supplementation, and (3) full field food supplementation. Both population numbers and dispersal rates of the second generation were higher under the third strategy. Macrolophus pygmaeus oviposits near food sources, therefore dispersal rates are higher when food is more spread out. Pest control was achieved in all treatments, but faster and at lower pest levels under the full field strategy.     

The influence of environmental features in the content of mycosporine‐like amino acids in red marine algae along the Brazilian coast

Mycosporine‐like amino acids (MAA) are ultraviolet screen substances synthesized by marine algae. The physiological function of these substances is related to cellular protection against UV radiation and as a protective mechanism against oxidative stress. These substances can be found mainly in the ocean, among red seaweeds. Its concentration in organisms has been related to ultraviolet radiation and availability of inorganic nitrogen in the environment. We start our study of MAA content in different species to understand if environmental conditions influence the concentration of MAAs in red seaweeds. The Brazilian coast presents abiotic factors that interact to create different physical‐chemical features in the environment. We collected 441 samples from 39 species of red seaweed easily found in the intertidal zone, in low tide, during the summer of 2015. The sampling encompassed a latitudinal gradient (3° S to 28°5′ S) at 23 points along the coast. We quantified and identified the content of MAAs in species through the method of high performance liquid chromatography. We detected for the first time the occurrence of MAAs in certain species of red algae that have not been reported to contain MAAs before. We confirmed that some environmental factors influenced the content of MAAs. Enhanced MAA contents, for example, were found in environments with a basic pH, a high ultraviolet index, and high concentrations of phosphate and nitrate. Salinity, dissolved oxygen and variations of sea surface temperature also influenced, in a secondary way, MAA content in algae in their natural environments.     

Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors

Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable EL_HDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.