International Journal of Global Community (Riksawan Institute - IJGC-RI)
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Changes in genetic architecture during relaxation in <i>Drosophila melanogaster </i>selected on divergent virgin life span
No full textArtificial selection experiments often confer important information on the genetic correlations constraining the evolution of life history. After artificial selection has ceased however, selection pressures in the culture environment can change the correlation matrix again. Here, we reinvestigate direct and correlated responses in a set of lines of Drosophila melanogaster that were selected on virgin life span and for which selection has been relaxed for 10 years. The decrease in progeny production in long-lived lines, a strong indication of antagonistic pleiotropy, had disappeared during relaxation. This was associated with a higher cost of reproduction to long-lived flies in mated, but not in virgin life span. These data strongly suggest that genetic mechanisms of mated and virgin life span determination are partly independent. Furthermore, data on body weight, developmental time and viability indicated deleterious effects of longevity selection in either direction, giving rise to a nonlinear relationship with life span for these characters. In order to reclaim original patterns, we founded a new set of derived lines by resuming selection in mixed replicate lines of the original set. Although selection was successful, most patterns in correlated characters remained, showing that these new patterns are resistant to new episodes of selection.</p
Interaction of targeted liposomes with primary cultured hepatic stellate cells:Involvement of multiple receptor systems
No full textBackground/Aims: In designing a versatile liposomal drug carrier to hepatic stellate cells (HSC), the interaction of mannose 6-phosphate human serum albumin (M6P-HSA) liposomes with cultured cells was studied.Methods: M6P-HSA was covalently coupled to the liposomal surface and the uptake and binding of 3H-labelled M6P-HSA liposomes by primary rat HSC and liver endothelial cells was determined. The targeting ability of M6P-HSA liposomes to HSC was tested in bile duct ligated rats using immunohistochemical methods.Results: The association of M6P-HSA liposomes with HSC was 4-fold higher than of control liposomes. An excess of M6P-HSA inhibited this association by 58%, indicating M6P receptor specificity. The scavenger receptor competitor polyinosinic acid abolished association of M6P-HSA liposomes with HSC. M6P-HSA liposomes also amply associated with endothelial cells, which abundantly express scavenger receptors. Endocytosis of M6P-HSA liposomes by HSC was temperature dependent and could be inhibited by monensin. In the fibrotic liver M6P-HSA liposomes co-localised with HSC.Conclusions: Coupling of M6P-HSA to liposomes strongly increases the in vitro uptake of these liposomes by HSC and endothelial cells. Both the mannose 6-phosphate receptor and the scavenger receptors are involved in the uptake process. M6P-HSA liposomes are potential drug carriers to HSC in the fibrotic liver. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</p
