Molecular modelling of protein-carbohydrate interactions. Understanding the specificities of two legume lectins towards oligosaccharides

By means of a series of new molecular modelling tools, the conformationalbehaviour of mannose-containing di- and trisaccharides boundto either concanavalin A or Lathyrus ochrus isolectin I (LOLI)has been assessed. Tools for estimating and analysing eitherthe ‘rigid’ or the ‘relaxed’ potentialenergy surfaces, representing the conformational space availablefor carbohydrates once interacting with lectins, are reportedfor the first time. Restrictions of conformational space arepredicted to occur with different magnitudes, depending on thenature of the glycosidic linkages, as well as the size of thecarbohydrates. Results from these molecular modelling studiesare compared to existing structural data. Not only could theobserved conformations and orientations of carbohydrates incrystalline lectin–oligosaccharides complexes be reproduced,but several other likely situations were also predicted to occur.Entropy calculations have been performed for comparison withexperimental thermodynamics data. The results of the simulationcan also help giving an explanation of some observed affinityconstants at the molecular level. concanavalin A Lathyrus ochrus lectin-oligosaccharide molecular modelling     

ANG II AT1 and AT2 receptors both inhibit bFGF-induced proliferation of bovine adrenocortical cells

Angiotensin II(ANG II) has long been known for its pressor and growth-promotingeffects, which are both mediated by theAT₁ receptor. By contrast, theAT₂ receptor has recently beenreported to mediate inhibition of proliferation through as yetundefined mechanisms. We report here that in bovine adrenal fasciculata cells ANG II by itself does not affect growth but inhibits basic fibroblast growth factor (bFGF)-induced DNA synthesis and blocks thecells in G₁ phase. Consistent withthis, ANG II inhibits cyclin D₁ expression and cyclinD₁-associated kinase activity. Theantimitogenic effect of ANG II is partly mimicked by theAT₂-selective agonist CGP-42112.It is also blocked partly and in an additive fashion by theAT₁- andAT₂-selective antagonists losartanand PD-123319, indicating the contribution of both receptor subtypes tothis response. AT₁-dependentantiproliferation is selectively blocked by the cyclooxygenaseinhibitor indomethacin and restored by prostaglandin E₂, whereasAT₂-receptor-mediated inhibitionof growth is suppressed by the tyrosine phosphatase inhibitorsorthovanadate and bpV(pic). Both pathways are, however,pertussis toxin sensitive. We hypothesize that, in fasciculatacells, the AT₁ receptor inhibitsbFGF-induced proliferation by stimulating prostaglandin synthesis,whereas the AT₂ receptor mediatesits effect through a pathway that requires protein tyrosine phosphataseactivation.

     

Larval Dispersal Modeling of Pearl Oyster Pinctada margaritifera following Realistic Environmental and Biological Forcing in Ahe Atoll Lagoon

Studying the larval dispersal of bottom-dwelling species is necessary to understand their population dynamics and optimize their management. The black-lip pearl oyster (Pinctada margaritifera) is cultured extensively to produce black pearls, especially in French Polynesia''s atoll lagoons. This aquaculture relies on spat collection, a process that can be optimized by understanding which factors influence larval dispersal. Here, we investigate the sensitivity of P. margaritifera larval dispersal kernel to both physical and biological factors in the lagoon of Ahe atoll. Specifically, using a validated 3D larval dispersal model, the variability of lagoon-scale connectivity is investigated against wind forcing, depth and location of larval release, destination location, vertical swimming behavior and pelagic larval duration (PLD) factors. The potential connectivity was spatially weighted according to both the natural and cultivated broodstock densities to provide a realistic view of connectivity. We found that the mean pattern of potential connectivity was driven by the southwest and northeast main barotropic circulation structures, with high retention levels in both. Destination locations, spawning sites and PLD were the main drivers of potential connectivity, explaining respectively 26%, 59% and 5% of the variance. Differences between potential and realistic connectivity showed the significant contribution of the pearl oyster broodstock location to its own dynamics. Realistic connectivity showed larger larval supply in the western destination locations, which are preferentially used by farmers for spat collection. In addition, larval supply in the same sectors was enhanced during summer wind conditions. These results provide new cues to understanding the dynamics of bottom-dwelling populations in atoll lagoons, and show how to take advantage of numerical models for pearl oyster management.