Comparison of intestinal permeability and p‐glycoprotein effects on the intestinal absorption of enantiomers of 2‐(2‐hydroxypropanamido) benzoic acid in rats

The purpose of this study was to compare intestinal permeability between enantiomers of 2‐(2‐hydroxypropanamido) benzoic acid ((R )‐/ (S )‐ HPABA), a marine‐derived antiinflammatory drug, using an in situ single‐pass intestinal perfusion (SPIP) model in rats. Concentrations, isolated regions of small intestine, and p ‐glycoprotein (P‐gp) inhibitor were performed to investigate their influences on the intestinal absorption of (R )‐/ (S )‐ HPABA. In addition, a molecular docking method was performed to illustrate our prediction. The absorption rate coefficients (K _a ) and permeability values (P _eff ) of (R )‐/ (S )‐ HPABA were calculated. The permeability of (S )‐HPABA was significantly (P <  0.01) higher than that of (R )‐HPABA in jejunum, and ileum permeability of (R )‐/ (S )‐ HPABA appeared best in ileum; the investigated concentrations ranged from 20 to 80 μg/mL, K _a and P _eff values of (R )‐/ (S )‐ HPABA increased linearly; in the presence of P‐gp inhibitor (verapamil), P _eff values of two enantiomers were increased significantly; and the effect of P‐gp on absorption of (R )‐HPABA is stronger than that of (S )‐HPABA in ileum segment. Based on these results, carrier‐mediated transport or passive transport combined with carrier‐mediated transport seems to be the mechanism for intestinal absorption of (R )‐/ (S )‐ HPABA, and (R )‐/ (S )‐ HPABA may be recognized as the P‐gp substrate. In addition, the intestinal permeability of (S )‐HPABA is higher than that of (R )‐HPABA.     

Data sharing across biobanks: epistemic values,data mutability and data incommensurability

Despite the centrality of epistemic issues in biobank knowledge generation, there is currently a lacuna in research addressing the epistemic assumptions of biobank science and data sharing. The article addresses this lacuna. Using the insights of philosophical and sociological analysis, we examine standardization and harmonization and central challenges biobank data-sharing faces. We defend two central epistemic values, namely “spatial and temporal translatability” and “epistemic adequacy” which foster effective biobank knowledge generation. The first refers to the way in which biobank data need to be re-usable and re-purposable by bioscience researchers who did not create them. Given the perennial issues of data mutability and incommensurability, we also propose “epistemic adequacy.” In uncovering the social and epistemic foundations of biobank science, we emphasize issues essential for achieving effective and transparent biobank practice and productive communication and engagement with the public about the nature, potential and limits of biobanks.     

Information content in data sets for a nucleated-polymerization model

We illustrate the use of statistical tools (asymptotic theories of standard error quantification using appropriate statistical models, bootstrapping, and model comparison techniques) in addition to sensitivity analysis that may be employed to determine the information content in data sets. We do this in the context of recent models [S. Prigent, A. Ballesta, F. Charles, N. Lenuzza, P. Gabriel, L.M. Tine, H. Rezaei, and M. Doumic, An efficient kinetic model for assemblies of amyloid fibrils and its application to polyglutamine aggregation, PLoS ONE 7 (2012), e43273. doi:10.1371/journal.pone.0043273.] for nucleated polymerization in proteins, about which very little is known regarding the underlying mechanisms; thus, the methodology we develop here may be of great help to experimentalists. We conclude that the investigated data sets will support with reasonable levels of uncertainty only the estimation of the parameters related to the early steps of the aggregation process.     

Novel Acyclonucleosides. Part 2. 2, 3-Dihydroxy-1-Methoxypropyl-and 3-Hydroxy-1-Methoxypropyl-Substituted Purines

Abstract

Novel purine nucleoside analogues in which the N-9 ribosyl moiety is replaced by a 2,3-dihydroxy-1-methoxypropyl or 3-hydroxy- 1-methoxy-propyl substituent and their N-7 substituted isomers have been synthesized and tested for antiviral activity.     

Studies of Hypervalent Iron

The iron (IV), (V) and (VI) oxidation states are of great interest because of their role in catalytic oxidation/ hydroxylation reactions. This report summarizes the information currently available on the kinetic and chemical properties of the water-soluble ions of FeO²₄-, FeO^3–₄ and FeO^4–₄, their prorogated forms. and/or simple complex derivatives. The discussion includes their radiation-induced formation, decay kinetics, reactivity with other compounds, determination of their respective pK_a, values as well as spectral properties.     

Topographically controlled thermal‐habitat differentiation buffers alpine plant diversity against climate warming

Aim We aim to: (1) explore thermal habitat preferences in alpine plant species across mosaics of topographically controlled micro‐habitats; (2) test the predictive value of so‐called ‘indicator values’; and (3) quantify the shift in micro‐habitat conditions under the influence of climate warming. Location Alpine vegetation 2200–2800 m a.s.l., Swiss central Alps. Methods High‐resolution infra‐red thermometry and large numbers of small data loggers were used to assess the spatial and temporal variation of plant‐surface and ground temperatures as well as snow‐melt patterns for 889 plots distributed across three alpine slopes of contrasting exposure. These environmental data were then correlated with Landolt indicator values for temperature preferences of different plant species and vegetation units. By simulating a uniform 2 K warming we estimated the changes in abundance of micro‐habitat temperatures within the study area. Results Within the study area we observed a substantial variation between micro‐habitats in seasonal mean soil temperature (ΔT = 7.2 K), surface temperature (ΔT = 10.5 K) and season length (>32 days). Plant species with low indicator values for temperature (plants commonly found in cool habitats) grew in significantly colder micro‐habitats than plants with higher indicator values found on the same slope. A 2 K warming will lead to the loss of the coldest habitats (3% of current area), 75% of the current thermal micro‐habitats will be reduced in abundance (crowding effect) and 22% will become more abundant. Main conclusions Our results demonstrate that the topographically induced mosaics of micro‐climatic conditions in an alpine landscape are associated with local plant species distribution. Semi‐quantitative plant species indicator values based on expert knowledge and aggregated to community means match measured thermal habitat conditions. Metre‐scale thermal contrasts significantly exceed IPCC warming projections for the next 100 years. The data presented here thus indicate a great risk of overestimating alpine habitat losses in isotherm‐based model scenarios. While all but the species depending on the very coldest micro‐habitats will find thermally suitable ‘escape’ habitats within short distances, there will be enhanced competition for those cooler places on a given slope in an alpine climate that is 2 K warmer. Yet, due to their topographic variability, alpine landscapes are likely to be safer places for most species than lowland terrain in a warming world.     

Illustrations pratiques – aspects pratiques et réglementaires

Quality and regulatory controls in hybrid nuclear medicine, layout and installations constraints, Diagnostic Reference values and regulatory and mandatory information in the medical report are presented in that part.     

Landscape structure and land use history influence changes in island plant composition after 100 years

Aim We investigated how current and historical land use and landscape structure affect species richness and the processes of extinction, immigration and species turnover. Location The northern part of the Stockholm archipelago, Baltic Sea, Sweden. We resurveyed 27 islands ranging from 0.3 to 33 ha in area. Methods We compared current plant survey data, cadastral maps and aerial photographs with records obtained from a survey in 1908, using databases and a digital elevation model to examine changes in plant community dynamics in space and time. We examined the effects of local and landscape structure and land use changes on plant species dynamics by using stepwise regression in relation to eight local and three landscape variables. The eight local variables were area, relative age, shape, soil heterogeneity, bedrock ratio, number of houses, forest cover change, and grazing 100 years ago. The three landscape variables were distance to mainland, distance to closest island with a farm 100 years ago, and structural connectivity. Hanski’s connectivity measure was modified to incorporate both connectivity and fragmentation. Results The investigated islands have undergone drastic changes, with increasing forest cover, habitation, and abandonment of grassland management. Although the total species richness increased by 31% and mean island area by 23%, we found no significant increase in species richness per unit area. Local variables explain past species richness (100 years ago), whereas both local and landscape variables explain current species richness, extinctions, immigrations and species turnover. Grazing that occurred 100 years ago still influences species richness, even though grazing management was abandoned several decades ago. The evidence clearly shows an increase in nitrophilous plant species, particularly among immigrant species. Main conclusions This study highlights the importance of including land use history when interpreting current patterns of species richness. Furthermore, local environment and landscape patterns affect important ecological processes such as immigration, extinction and species turnover, and hence should be included when assessing the impact of habitat fragmentation and land use change. We suggest that our modified structural connectivity measure can be applied to other types of landscapes to investigate the effects of fragmentation and habitat loss.