Discovery of a potent and brain penetrant mGluR5 positive allosteric modulator

This Letter describes the discovery of a novel series of mGluR5 positive allosteric modulators (PAMs). The lead compound, 11c, exhibits excellent potency (EC₅₀ = 30 nM) in vitro, and reaches high brain levels in both rats and mice after oral administration.     

Fully informative microsatellite markers for the tetraploid plant Eritrichium nanum (Boraginaceae)

We characterized eight polymorphic, codominant nuclear microsatellite loci in the tetraploid plant Eritrichium nanum. The different allelic configurations occurring under tetrasomic inheritance were fully resolved at all loci. Two natural populations showed high observed heterozygosities, which were in agreement with Hardy-Weinberg expectations. There was no evidence of genetic linkage disequilibrium for any pair of loci. The results suggest that these microsatellite markers are useful for mating system and population genetic analyses in high-alpine E. nanum.     

Utility of multilocus genotypes for taxon assignment in stands of closely related European white oaks from Switzerland

Background and Aims

European white oaks (Quercus petraea, Q. pubescens, Q. robur) have long puzzled plant biologists owing to disputed species differentiation. Extensive hybridization or shared ancestry have been proposed as alternative hypotheses to explain why genetic differentiation between these oak species is low. Species delimitation is usually weak and often shows gradual transitions in leaf morphology. Hence, individual identification may be difficult, but remains a critical step for both scientific work and practical management.

Methods

Multilocus genotype data (five nuclear microsatellites) were used from ten Swiss oak stands for taxon identification without a priori grouping of individuals or populations, using model-based Bayesian assignment tests.

Key Results

Three groups best structured the data, indicating that the taxonomical signal was stronger than the spatial signal. Most individuals showed high posterior probabilities for either of three genetic groups that were best circumscribed as taxonomical units. The assignment of a subset of trees, whose taxonomic status had been previously characterized in detail, supported this classification scheme.

Conclusions

Molecular-genetic assignment tests are useful in the identification of species status in critical taxon complexes such as the European white oaks. Such an approach is of practical importance for forest management, e.g. for stand certification or in seed trade to trace the origin of forest products.Key words: Assignment test, Bayesian inference, multilocus genotype, nuclear microsatellites, Quercus sp., species complex     

Flower nitrogen status and populations of Frankliniella occidentalis feeding on Lycopersicon esculentum

Alighting and capture of wild olive fruit flies, Bactrocera oleae (Rossi) (Diptera, Tephritidae), on spheres of seven different colours was studied on Chios island, Greece. The 70-mm-diam plastic spheres, coated with adhesive, were suspended on olive trees. Yellow and orange spheres trapped the greatest number of males while red and black spheres trapped the greatest number of females. White and blue spheres were the least effective for both sexes. Peak captures occurred in the late afternoon and especially around sunset. Since mating takes place in the last hours of the photophase, the increased captures during that period may be related to the sexual behaviour of the fly. When red spheres were assessed against glass McPhail traps baited with 2% ammonium sulphate, which consist a standard tool for monitoring the olive fruit fly in Greece, there were no significant differences in male captures. However, spheres trapped almost three times as many females as McPhail traps. The possible mechanisms underlying colour discrimination, the motivation of alighting flies and the possible use of red spheres for monitoring and controlling B. oleae are discussed.     

6-(4-Benzylpiperazin-1-yl)benzodioxanes as selective ligands at cloned primate dopamine D(4) receptors.

A series of novel 6-(4-benzylpiperazin-1-yl)benzodioxanes were prepared and screened at selected dopamine receptor subtypes. 6-(4-[4-Chlorobenzyl]piperazin-1-yl)benzodioxane (2d) had high affinity and selectivity for the D₄ dopamine receptor subtype and was identified as a D₄ antagonist via its attenuation of dopamine-induced GTPγ³⁵S binding at the D₄ receptor.     

Molecular identification of fine roots of trees from the Alps: reliable and fast DNA extraction and PCR-RFLP analyses of plastid DNA

Fine roots of trees are intensively used as indicators to assess soil alterations, e.g. those owing to atmospheric inputs of acidifying substances, but their identification to species with morphological criteria is difficult. In this study, we established molecular techniques in order to identify fine roots of the 30 most common tree species of the Alps. We developed a protocol for efficient isolation of DNA from fine roots with extraction of DNA in the presence of polyvinylpyrrolidone (PVP) and polyvinylpolypyrrolidone (PVPP). The trnL (UAA) intron of plastid DNA was used as a marker for fine root identification. We amplified and sequenced this intron with plant universal primers. The size of the sequences ranged from 444 to 672 bp. A synoptic key for species identification was designed on the basis of restriction fragment patterns predicted from sequence data. Using the restriction enzyme TaqI as key enzyme, and where necessary HinfI, RsaI and CfoI, 16 taxa, including Picea abies, Larix decidua, Abies alba, and Fagus sylvatica, the dominant tree species of the Alpine region could be identified by agarose gel electrophoresis of restriction fragments. Fourteen taxa could be identified to the genus level, among them Quercus, Salix and Populus species. In a field study, conducted in a 20 x 30 m plot of a mixed forest with five tree species, fine roots of 43 out of 46 samples were identified and their distributions were mapped. These results demonstrate the utility of our DNA extraction method and of the trnL intron for the identification of fine tree roots.     

Serglycin proteoglycan synthesis in the murine uterine decidua and early embryo

This study has explored the localization and synthesis of the serglycin proteoglycan in the murine embryo and uterine decidua during midgestation. Embryos in deciduae were subjected to in situ hybridization with cRNA probes and to immunohistochemical detection with a specific antibody against murine serglycin. Adherent decidual cell cultures were prepared from freshly isolated deciduae. Proteoglycan biosynthesis was investigated by labeling intact deciduae and decidual cultures with (35)S-sulfate. Serglycin mRNA was detected by in situ hybridization throughout the mesometrial portion and at the periphery of the antimesometrial portion of the decidua at Embryonic Day (E) 8.5, and in the parietal endoderm surrounding the embryo. Serglycin mRNA was detected in fetal liver at E11.5-E14.5. Serglycin was detected by immunohistochemistry in decidua and parietal endoderm at E8.5 and in liver at E13.5. Most of the proteoglycans synthesized by cultured intact deciduae (78%) and adherent decidual cultures (91%) were secreted into the medium. Serglycin proteoglycan may play an important role in uterine decidual function during early postimplantation development.     

Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 1: identification and structure-activity relationships

Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 7b. Their related synthesis was also reported.     

Design, synthesis, and discovery of 3-piperazinyl-3,4-dihydro-2(1H)-quinolinone derivatives: a novel series of mixed dopamine D2/D4 receptor antagonists

3-Piperazinyl-3,4-dihydro-2(1H)-quinolinone derivatives (delta-lactams) were designed, synthesized, and identified as a new series of mixed dopamine D2/D4 receptor antagonists. To further the structure-activity relationship (SAR) study, 3-piperazinylindolin-2-ones (gamma-lactams) and 3-piperazinyl-3H,4H,5H-benzo[f]azepin-2-ones (epsilon-lactams) were also prepared and examined.