Synergistic effect of hypoglycemic sulfonylureas and negative phospholipids on calcium transport: ionic and conformational aspects.

peer reviewedIn a two-phase bulk system for the study of ionophoresis, the capacity of hypoglycemic sulfonylureas to translocate Ca2+ was enhanced in a synergistic manner by negatively charged phospholipids. High concentrations of Na+ or K+ had relatively little effect on sulfonylurea-mediated Ca2+ translocation. The acidity constant of hypoglycemic sulfonylureas ranged from 10(-5) to 10(-6). The conformation analysis of Ca2+ -gliquidone complexes with a 1:1 or 1:2 stoichiometry and of a hybrid complex between Ca2+ and both gliquidone and phosphatidylserine revealed configurations suitable for Ca2+ transport across a hydrophobic domain. These findings raise the possibility that the cationic response of the pancreatic B-cell to hypoglycemic sulfonylureas may be due primarily to an alteration of both Ca2+ and H+ transport

A gene graveyard in the genome of the fungus Podospora comata

WOS:000457456800015International audienceMechanisms involved in fine adaptation of fungi to their environment include differential gene regulation associated with single nucleotide polymorphisms and indels (including transposons), horizontal gene transfer, gene copy amplification, as well as pseudogenization and gene loss. The two Podospora genome sequences examined here emphasize the role of pseudogenization and gene loss, which have rarely been documented in fungi. Podospora comata is a species closely related to Podospora anserina, a fungus used as model in several laboratories. Comparison of the genome of P. comata with that of P. anserina, whose genome is available for over 10 years, should yield interesting data related to the modalities of genome evolution between these two closely related fungal species that thrive in the same types of biotopes, i.e., herbivore dung. Here, we present the genome sequence of the mat+isolate of the P. comata reference strain T. Comparison with the genome of the mat+isolate of P. anserina strain S confirms that P. anserina and P. comata are likely two different species that rarely interbreed in nature. Despite having a 94-99% of nucleotide identity in the syntenic regions of their genomes, the two species differ by nearly 10% of their gene contents. Comparison of the species-specific gene sets uncovered genes that could be responsible for the known physiological differences between the two species. Finally, we identified 428 and 811 pseudogenes (3.8 and 7.2% of the genes) in P. anserina and P. comata, respectively. Presence of high numbers of pseudogenes supports the notion that difference in gene contents is due to gene loss rather than horizontal gene transfers. We propose that the high frequency of pseudogenization leading to gene loss in P. anserina and P. comata accompanies specialization of these two fungi. Gene loss may be more prevalent during the evolution of other fungi than usually thought