Small conductance calcium-activated K+ channels, SkCa, but not voltage-gated K+ (Kv) channels, are implicated in the antinociception induced by CGS21680, a A2A adenosine receptor agonist

It has been shown that A2A adenosine receptors are implicated in pain modulation. The precise mechanism by which activation of A2A receptors produces analgesic effects, however, remains unclear. The aim of this study was to investigate the possible involvement of apamin-sensitive calcium-activated potassium channels (SKCa) and voltage-gated potassium (Kv) channels in A2A receptor activation-induced analgesic effects. Using mice, we evaluated the influence of apamin, a non specific blocker of SKCa channels, Lei-Dab7 (an analog of scorpion Leiurotoxin), a selective blocker of SKCa2 channels, and kaliotoxin (KTX) a Kv channel blocker, on the CGS 21680 (A2A adenosine receptor agonist)-induced increases in hot plate and tail pinch latencies. All drugs were injected in mice via the intracerebroventricular route. We found that apamin and Lei-Dab7, but not KTX, reduced antinociception produced by CGS21680 on the hot plate and tail pinch tests in a dose dependent manner. Lei-Dab 7 was more potent than apamin in this regard. We conclude that SKCa but not Kv channels are implicated in CGS 21680-induced antinociception.     

Action versus result-oriented schemes in a grassland agroecosystem: a dynamic modelling approach

Effects of agri-environment schemes (AES) on biodiversity remain controversial. While most AES are action-oriented, result-oriented and habitat-oriented schemes have recently been proposed as a solution to improve AES efficiency. The objective of this study was to compare action-oriented, habitat-oriented and result-oriented schemes in terms of ecological and productive performance as well as in terms of management flexibility. We developed a dynamic modelling approach based on the viable control framework to carry out a long term assessment of the three schemes in a grassland agroecosystem. The model explicitly links grazed grassland dynamics to bird population dynamics. It is applied to lapwing conservation in wet grasslands in France. We ran the model to assess the three AES scenarios. The model revealed the grazing strategies respecting ecological and productive constraints specific to each scheme. Grazing strategies were assessed by both their ecological and productive performance. The viable control approach made it possible to obtain the whole set of viable grazing strategies and therefore to quantify the management flexibility of the grassland agroecosystem. Our results showed that habitat and result-oriented scenarios led to much higher ecological performance than the action-oriented one. Differences in both ecological and productive performance between the habitat and result-oriented scenarios were limited. Flexibility of the grassland agroecosystem in the result-oriented scenario was much higher than in that of habitat-oriented scenario. Our model confirms the higher flexibility as well as the better ecological and productive performance of result-oriented schemes. A larger use of result-oriented schemes in conservation may also allow farmers to adapt their management to local conditions and to climatic variations.     

Food choice and food competition among the three major primate species of French Guiana

The three most important primates of French Guiana are frugivorous species, but to different degrees. Ateles paniscus is almost exclusively frugivorous, Alouatta seniculus frugivorous-folivorous, and Cehus apellu partially insectivorous; thus, the overall specific diet spectra arc well separated. During the season when fruit production is minimal, fruit intake by all species is also minimal which results in the greatest diversities in diet and the lowest diet overlaps. Real competition for the common main food category, i.e. fruits, only occurs during the most favourable period. Nevertheless, some fruit characteristics (e.g. size…) separate the monkey species from each other in fruit choice and make the interspecific competition of little importance.     

The influence of soil cover organization on the floristic and structural heterogeneity of a Guianan rain forest

The impact of soil cover organization on the forest community has been studied in a 19-ha tract at Piste de St Elie station in French Guiana. 195 species each represented by at least 10 individuals were chosen from records of the position, diameter at breast height (dbh) and precise identification by botanical sampling of 12104 ligneous plants (dbh 10 cm).Spatial variations in the soil were mapped using the method proposed by Boulet et al. (1982). The soil mapping units correspond to the successive stages of evolution of a currently unbalanced ferralitic cover. These stages describe firstly the thinning by erosion of the microaggregated upper horizon and secondly the mineralogical changes under more or less extended hydromorphic conditions. The degree of evolution of ferralitic cover is also related to the hydrodynamic functioning and chemical properties of the soil. Geological substrate, topography and slope have also been taken into account.Analysis of the influence of environmental variables on plant cover has been performed using the Ecological Profiles method and Correspondence Analysis (CA) of the table of ecological profiles.The forest community seems to be dependent on the soil and the topographical features that govern it. There are significant, exclusive soil-species links for each soil functioning mapping unit. However, the highest proportion of significant positive links is connected with a thick microaggregated horizon (25%). Several species are of real value as indicators and more particularly enable differentiation between the forest stands of typical ferralitic soil and the ones of thinned out, transformed and hydromorphic soils. The CA of the species by environmental variables matrices reveals two significant factorial axes. The first can be associated with the drainage mainly related to the thinning of the soil and the second with the hydromorphic conditions related to the topography. The vegetation ordination of the stands ( 0.25 ha) delimited in the various soil domains clearly shows that changes in ferralitic cover and in particular the transition from soil with deep vertical drainage to soil with superficial lateral drainage is accompanied by substantial changes in the forest community.     

How are sticky chromosomes formed?

Blood lymphocytes in culture were irradiated by gamma-rays 3 h to 30 mn before harvesting. The various induced lesions were analysed, with a particular attention on sticky chromosomes, i.e. radial figures in which chromosomes are not obviously broken, but are linked by a tiny filament. Such anomalies are preferentially induced in mid to late G2-phase. They result from recombinations occurring at nonrandom chromosome regions: junction between hetero- and euchromatin, and telomeric regions. It is proposed that they are formed when double strand breaks are induced while intrachromatidic links have started to be formed in the course of chromosome condensation. If this interpretation is correct, the apparent lack of induced breakage of premitotic chromosomes is artifactual.     

Molecular modeling and docking simulations of scorpion toxins and related analogs on human SKCa2 and SKCa3 channels

The small-conductance Ca2+-activated K+ (SKCa) channels modulate cytosolic Ca2+ concentration in excitable and non-excitable tissues by regulating the membrane potential and are responsible of slow action potential after hyperpolarization that inhibits cell firing. Among these, human SKCa2 and SKCa3 channels differ in the pore region by only two residues: Ala331 and Asn367 (human small-conductance calcium-activated potassium channel, hSKCa2) instead of Val485 and His521 (hSKCa3). To design highly selective blockers of hSKCa channels, a number of known hSKCa2 and/or hSKCa3-active peptides (i.e. scorpion toxins and analogs thereof) were analyzed for their interactions and selectivities toward these channels. Molecular models of hSKCa2 and hSKCa3 channels (S5-H5-S6 portion) were generated, and scorpion toxins/peptides of unsolved three-dimensional (3D) structures were modeled. Models of toxin-channel complexes were generated by the bimolecular complex generation with global evaluation, and ranking (BiGGER) docking software and selected by using a screening method of the docking solutions. A high degree of correlation was found to exist between docking energies and experimental Kd values of peptides that blocked hSKCa2 and/or hSKCa3 channels, suggesting it could be appropriate to predict Kd values of other bioactive peptides. The best scoring complexes were also used to identify key residues of both interacting partners, indicating that such an approach should help the design of more active and/or selective peptide blockers of targeted ion channels.     

Maurotoxin and the Kv1.1 channel: voltage-dependent binding upon enantiomerization of the scorpion toxin disulfide bridge Cys31-Cys34.

Maurotoxin (MTX) is a 34-amino acid polypeptide cross-linked by four disulfide bridges that has been isolated from the venom of the scorpion Scorpio maurus palmatus and characterized. Maurotoxin competed with radiolabeled apamin and kaliotoxin for binding to rat brain synaptosomes and blocked K+ currents from Kv1 channel subtypes expressed in Xenopus oocytes. Structural characterization of the synthetic toxin identified half-cystine pairings at Cys3-Cys24, Cys9-Cys29, Cys13-Cys19 and Cys31-Cys34 This disulfide bridge pattern is unique among known scorpion toxins, particularly the existence of a C-terminal '14-membered disulfide ring' (i.e. cyclic domain 31-34), We therefore studied structure-activity relationships by investigating the structure and pharmacological properties of synthetic MTX peptides either modified at the C-terminus ?i.e. MTX(1-29), [Abu31,34]-MTX and [Cys31,34, Tyr32]D-MTX) or mimicking the cyclic C-terminal domain [i.e. MTX(31-34)]. Unexpectedly, the absence of a disulfide bridge Cys31-Cys34 in [Abu 31,34]-MTX and MTX(1-29) resulted in MTX-unrelated half-cystine pairings of the three remaining disulfide bridges for the two analogs, which is likely to be responsible for their inactivity against Kv1 channel subtypes. Cyclic MTX(31-34) was also biologically inactive. [Cys31,34, Tyr32]D-MTX, which had a 'native', MTX-related, disulfide bridge organization, but a D-residue-induced reorientation of the C-terminal disulfide bridge, was potent at blocking the Kv1.1 channel. This peptide-induced Kv1.1 blockage was voltage-dependent (a property not observed for MTX), maximal in the low depolarization range and associated with on-rate changes in ligand binding. Thus, the cyclic C-terminal domain of MTX seems to be crucial for recognition of Kv1.3, and to a lesser extent, Kv1.2 channels and it may contribute to the stabilization and strength of the interaction between the toxin and the Kv1.1 channel.