Flunitrazepam Binding to Intact and Homogenized Astrocytes and Neurons in Primary Cultures

[3H]Flunitrazepam binds to intact and homogenized mouse astrocytes and neurons in primary cultures. In intact cells, the binding is to a single, high-affinity, saturable population of benzodiazepine binding sites with a KD of 7 nM and Bmax of 6,033 fmol/mg protein in astrocytic cells and a KD of 5 nM and Bmax of 924 fmol/mg protein in neurons. After homogenization, the Bmax values decrease drastically in both cell types, but most in astrocytes. The temperature and time dependency are different for the two cell types, with a faster association and dissociation in astrocytes than in neurons and a greater temperature sensitivity in the astrocytes. Moreover, flunitrazepam binding sites on neuronal and astrocytic cells have different pharmacological profiles. In intact astrocytic cells, Ro 5-4864 (Ki = 4 nM) is the most potent displacing compound, followed by diazepam (Ki = 6 nM) and clonazepam (Ki = 600 nM). In intact neurons, the relative order of potency of these three compounds is different: diazepam (Ki = 7 nM) is the most potent, followed by clonazepam (Ki = 26 nM) and Ro 5-4864, which has little effect. After homogenization the potency of diazepam decreases. We conclude that both neuronal and astrocytic cells possess high-affinity [3H]flunitrazepam binding sites. The pharmacological profile and kinetic characteristics differ between the two cell types and are further altered by homogenization.     

Synthesis of α-trifluoromethyl α-amino acids with aromatic, heteroaromatic and ferrocenyl subunits in the side chain

Summary. 5-Benzyloxy-4-trifluoromethyl-1,3-oxazoles, obtained from 5-fluoro-4-trifluoromethyloxazoles and benzyl alcohols, are capable for rearrangements. A 1,3 shift of a benzyl group is the key step of a new general route toward α-trifluoromethyl substituted aromatic and heteroaromatic amino acids, demonstrating that 5-fluoro-4-trifluoromethyl-1,3-oxazole is a synthetic Tfm-Gly equivalent. On reaction with benzpinacol partially fluorinated oxazoles are transformed into bis(trifluoromethyl) substituted 2,5-diamino adipic acid and N-benzoyl-2-benzhydryl-3,3,3-trifluoroalanine.     

Adult life spans of butterflies (Lepidoptera: Papilionoidea + Hesperioidea): broadscale contingencies with adult and larval traits in multi-species comparisons

Adult life spans of insects are part of supposedly adaptive life-history syndromes, which involve a variety of reproductive strategies with regard to mating, egg maturation and egg laying. Contingencies of life span with many other morphological, behavioural, and ecological traits are to be expected. We used a data-mining approach, incorporating controls for phylogeny, to uncover broad patterns of trait contingencies in a literature-derived data set of adult life spans for 350 butterfly species. We found that adult feeding habit has strong links with life spans, with pollen-feeders living longer than fruit feeders, which in turn live longer than nectar feeders. Furthermore, traits reducing susceptibility to predators (i.e. aposematism, eye-spots) are associated with longer life. Mud-puddling behaviour as a means of gaining access to minerals, and possibly nitrogen, was generally associated with a short life. We also found strong impacts of the region of occurrence of species (i.e. whether they were tropical or temperate taxa), but received conflicting results depending on whether we analysed field data (longer life in the tropics) or data from caged individuals (shorter life in the tropics). Adult longevity was associated with the growth form of larval host plants (higher on lianas as opposed to herbs, shrubs, or trees), whereas other larval host plant traits did not have strong links with species' life spans. We discuss the hypothetical evolutionary mechanisms explaining those patterns and suggest predictions that could be tested in further research.  © 2009 The Linnean Society of London, Biological Journal of the Linnean Society , 2009, 96 , 166–184.     

Group differences in the heritability of items and test scores

It is important to understand potential sources of group differences in the heritability of intelligence test scores. On the basis of a basic item response model we argue that heritabilities which are based on dichotomous item scores normally do not generalize from one sample to the next. If groups differ in mean ability, the functioning of items at different ability levels may result in group differences in the heritability of items, even when these items function equivalently across groups and the heritability of the underlying ability is equal across groups. We illustrate this graphically, by computer simulation, and by focusing on several problems associated with a recent study by Rushton et al. who argued that the heritability estimates of items of Raven''s Progressive Matrices test in North-American twin samples generalized to other population groups, and hence that the population group differences on this test of general mental ability (or intelligence) had a substantial genetic component. Our results show that item heritabilities are strongly dependent on the group on which the heritabilities were based. Rushton et al.''s results were artefactual and do not speak to the nature of population group differences in intelligence test performance.     

Body size frequency distributions in African mammals are bimodal at all spatial scales

Aim  To examine frequency distributions of body sizes for mammal assemblages at several spatial scales and assess the generality of results heretofore obtained only for North and South America.
Location  Africa.
Methods  Terrestrial African mammals were allocated to major biomes, and regional and local assemblages were extracted from published and unpublished literature. We produced body size frequency distributions for local, regional, biomic and continental distributions, both for whole assemblages and for three foraging strata, and compared these with several standard metrics (e.g. mean and median size, interquartile range, skew, bimodality, etc.). Differences between distributions were quantified using t -tests and analysis of variance.
Results  African mammal faunas exhibit features in common with those of North and South America, most notably the gradual reduction in the modality and skew of body size distributions with decreasing spatial scale. Unlike other continents, however, the African mammal fauna exhibits a bimodal frequency distributions at all spatial scales. Our data suggest a role for competitive interactions in local assembly, as documented elsewhere, but further data on locally interacting assemblages are needed.
Main conclusions  The African fauna appears unique in the expression of bimodality at all spatial scales. The presence of a secondary mode at large body size may reflect co-evolutionary adjustments to proto-human hunters and consequent escape from anthropogenic Pleistocene extinctions, but the absence of species of intermediate body size ( c . 250–4000 g) remains anomalous and is not readily explained by either historical or modern (ecological) factors. For the African mammal fauna, a key question in understanding the role of history versus ecology may not be why there are so many large species, but why there are so few intermediate-sized species.     

Soil Temperature, Not Aboveground Plant Productivity, Best Predicts Intra-Annual Variations of Soil Respiration in Central Iowa Grasslands

Soil respiration (R_SOIL) is the second largest carbon flux between terrestrial systems and the atmosphere, with a magnitude 10 times greater than anthropogenic carbon dioxide production. Therefore, it is important that we understand, and be able to predict, how R_SOIL responds to climate change. Although a positive, significant temperature effect on R_SOIL has long been recognized, recent studies emphasize the overriding importance of current photosynthesis in controlling R_SOIL. We tested the hypothesis that model inclusion of intra-annual variations in aboveground net primary productivity (ANPP) significantly improves R_SOIL estimates over predictions based on soil temperature alone. We also evaluated the possibility that canopy production is less directly linked to R_SOIL, by testing the hypothesis that intersite differences in R_SOIL correlate more strongly with root biomass than with ANPP. We tested these hypotheses by measuring R_SOIL, ANPP, and root biomass at four Iowa grasslands that differed in aboveground growth phenology and productivity. Among all sites, intra-annual variations in R_SOIL were most strongly related to soil temperature (R ² = 0.89), not ANPP (R ² = 0.53). All sites responded identically to changes in soil temperature (site-by-temperature P = 0.53), but inconsistently to variation in aboveground dynamics (site-by-canopy P < 0.0001). Incorporating canopy dynamics into temperature-based predictive models improved model R ² by a maximum of 0.01. Among-site differences in R_SOIL were related to root biomass (P < 0.001) but not ANPP (P = 0.34). We found no useful linkage between canopy characteristics and intra-annual or site-specific R_SOIL predictions, perhaps because shoot and root dynamics were not consistently linked through time or among sites.     

Closed testing procedures for group sequential clinical trials with multiple endpoints

A simple approach is given for conducting closed testing in clinical trials with multiple endpoints in which group sequential monitoring is planned. The approach allows a flexible stopping time; the earliest and latest stopping times are described. The paradigm is applicable both to clinical trials with multiple endpoints and to the one-sided multiple comparison problem of several treatments versus a control. The approach leads to enhancements of previous methods and suggestions for new methods. An example of a respiratory disease trial with four endpoints is given.     

Non‐angiosperm phytochromes and the evolution of vascular plants

The phytochromes, a class of plant light‐sensing pigments, are a gene family with a long, complex evolutionary history. Angiosperms each have five or more phytochromes (designated A to E in Arabidopsis ) with distinct functions as light receptors and only moderate sequence identities for different types within a species. The long‐term challenge taken up here is to trace the origin and function of the various motifs within the angiosperm phytochromes through gymnosperm phytochromes (types N, O and P) and lower plant phytochromes, sometimes reaching even to bacterial progenitor molecules. Particularly intriguing are the findings of homology of a C‐terminal region of phytochromes with bacterial transmitter modules and of a large N‐terminal region with a protein encoded by a gene from the cyanobacterum Synechocystis . Phylogenetic analysis helps to answer general questions such as the times of divergence of mono‐ and dicotyledons, of groups of gymnosperms or of ferns. Phytochrome sequences suggest (1) that mono‐ and dicotyledons became separated 150‐200 million years earlier than indicated by the fossil record and (2) that Ginkgo and Cycas have been separated unexpectedly late from the lineage giving rise to the Pinidae. (3) The status of Psilotum as a close relative of the primeval vascular plants is not supported. Phytochrome gene sequences additionally reveal that (4) moss and fern phytochromes have erratically acquired C‐termini which, though kinase‐like, are different from the common ones and that (5) introns have been lost, gained or shifted in position from algae to angiosperms. Phytochromes promise to be a rich source of phylogenetic information into the future as more sequences and functional data emerge, not least from studies of lower plants.