Promotion of sustainable capture fisheries and aquaculture in Asian reservoirs and lakes

A collaborative international project funded by the European Union's INCO-DC programme is undertaking limnological, fish biological, environmental and socio-economic research in five tropical lakes and reservoirs in Sri Lanka, Thailand and the Philippines over the period 1998–2001. The aim is to determine their trophic structure and their capacity to sustain both their existing fisheries and present and future aquaculture. In some cases, these activities could potentially be expanded for the benefit of rural communities and of the local market within the bounds of social and environmental sustainability. This paper describes the concepts and methods involved in this innovative multidisciplinary project which aims to integrate limnological, fisheries and socio-economic issues in a comparative approach involving Asian and European research teams.Deceased.     

The insulin-like growth factor axis in cell cycle progression.

Emerging evidence suggests that members of the Insulin-like Growth Factors (IGFs) family, including IGF-I, IGF-II, the IGF-I receptor (IGF-IR), and the IGF-binding proteins (IGFBPs) play a central role in the development and progression of cancer. Cancer cells exhibit an increased and deregulated proliferative activity. Abnormalities in many positive and negative modulators of the cell cycle are also frequent in many cancer types. Recent advances in the understanding of cell-cycle control mechanisms have been applied to outline the molecular mechanism through which IGFs regulate cell cycle progression. In this review, we will provide a brief overview of the role of the IGF system as a regulator of some components of the cell cycle.     

Expression of a bacterial gene turned on by a potent carcinogen.

Contrary to mutagenesis, lysogenic induction produced by chemical carcinogens occurs in the majority of a population of lysogenic cells. Such a mass effect can therefore be measured at the biochemical level using an E. coli tester strain in which the galactose operon has been put under the negative control of the lambda repressor. In this publication we show that galactokinase synthesis is turned on by aflatoxin B1 metabolites within an hour after treatment of the tester bacteria. Such a biochemical assay provides a useful means for identifying potential chemical carcinogens.     

Interaction between cystatin-derived peptides and papain

The interaction between papain and synthetic peptides which tentatively mimic cystatin surfaces was investigated both enzymatically and structurally. Measurements of dissociation equilibrium constants for the interaction of papain with these peptides modified by successive deletions or substitutions demonstrated that the QVVAG segment, which is highly conserved throughout members of the cystatin superfamily, is essential for the interaction. The glycylcontaining (N-terminal) fragments and PW-containing (C-terminal) fragments were found to be of lesser importance, since each could be deleted without significantly modifying the interaction. These fragments improved the stability of the interacting QVVAG region, which appeared to be substrate-like in all peptides tested, as it was cleaved at the A-G bond upon peptide-papain interaction. Replacement of the A residue at the scissile bond of the QVVAG by a blocked cysteinyl residue reduced the rate of cleavage of the susceptible bond and therefore shifted the resulting peptide from a substrate to an inhibitor. Derivatization of this substituted peptide at its N- and C-terminal ends by fluoresceinyl groups resulted in a dramatic decrease in theK _i to 0.5 µM. This improvement in the inhibitory properties of the substituted and derivatized peptides was correlated with structural changes as analyzed by molecular dynamic calculations. The results were compared to those proposed for the mechanism of inhibition by natural inhibitors of the cystatin superfamily.     

Osteopromotion of Biphasic Calcium Phosphate granules in critical size defects after osteonecrosis induced by focal heating insults

Heat-induced osteonecrosis represents a simple, rapid, and inexpensive method for reproducing the effects of bone disease. In the present study, we employed this technique to induce osteonecrosis in femoral defects in rabbits and assessed the efficacy of treatment using Biphasic Calcium Phosphate (BCP) granules (MBCP+?, Biomatlante SA). After 3 weeks, the osteopromotion effects of BCP granules could be statistically proven (P < 0.05) through image analysis of newly formed bone in osteonecrosed sites containing BCP granules when compared to empty control sites. Increasing mature and woven bone presence was observed after 6 and 12 weeks, forming new trabeculae in necrosed site. Significant statistical differences were evidenced at each time between empty necrosed and filled necrosed defects in terms of new bone volume.     

A nuclear magnetic resonance study of the interactions of antimalarial drugs with porphyrins

Haematins (hydroxyferriprotoporphyrin IX) constitute a possible receptor for antimalarial drugs such as chloroquine or quinine. This paper reports the study of the interactions of these two molecules with two tetrapyrrole (haematin and uroporphyrin I) by 1H-NMR spectroscopy. This method provided us with the geometry of the interactions in aqueous medium. The interaction consists of a close stacking of the porphyrin ring and the quinoleine moiety of the drugs. Using a porphyrin ring current model it was possible to reach the spatial relationships of the interacting species. It was concluded that hydrophobic forces play a key role in the interaction. The porphyrin plane can accommodate wide structural variations of the interacting species, leading to a weak specificity. The consequences on the mode of action of antimalarial drugs are discussed.     

Structure-based design and synthesis of macrocyclic human rhinovirus 3C protease inhibitors

The design and synthesis of macrocyclic inhibitors of human rhinovirus 3C protease is described. A macrocyclic linkage of the P1 and P3 residues, and the subsequent structure-based optimization of the macrocycle conformation and size led to the identification of a potent biochemical inhibitor 10 with sub-micromolar antiviral activity.     

Identification of Ca<Superscript>2+</Superscript> signaling components in neural stem/progenitor cells during differentiation into neurons and glia in intact and dissociated zebrafish neurospheres

The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the development, plasticity and regeneration of the CNS, and the recent development of reliable protocols for isolating and culturing neural stem/progenitor cells (NSCs/NPCs) from the brain of adult fish now enables the exploration of mechanisms underlying the induction/specification/differentiation of these cells. Here, we refined a protocol to generate proliferating and differentiating neurospheres from the entire brain of adult zebrafish. We demonstrated via RT-qPCR that some isoforms of ip3r, ryr and stim are upregulated/downregulated significantly in differentiating neurospheres, and via immunolabelling that 1,4,5-inositol trisphosphate receptor (IP₃R) type-1 and ryanodine receptor (RyR) type-2 are differentially expressed in cells with neuron- or radial glial-like properties. Furthermore, ATP but not caffeine (IP₃R and RyR agonists, respectively), induced the generation of Ca²⁺ transients in cells exhibiting neuron- or glial-like morphology. These results indicate the differential expression of components of the Ca²⁺-signaling toolkit in proliferating and differentiating cells. Thus, given the complexity of the intact vertebrate brain, neurospheres might be a useful system for exploring neurodegenerative disease diagnosis protocols and drug development using Ca²⁺ signaling as a read-out.