Étude des marqueurs génétiques sanguins dans deux races de poneys de pologne

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Molecular Recognition of H3/H4 Histone Tails by the Tudor Domains of JMJD2A: A Comparative Molecular Dynamics Simulations Study

Background: Histone demethylase, JMJD2A, specifically recognizes and binds to methylated lysine residues at histone H3 and H4 tails (especially trimethylated H3K4 (H3K4me3), trimethylated H3K9 (H3K9me3) and di, trimethylated H4K20 (H4K20me2, H4K20me3)) via its tandem tudor domains. Crystal structures of JMJD2A-tudor binding to H3K4me3 and H4K20me3 peptides are available whereas the others are not. Complete picture of the recognition of the four histone peptides by the tandem tudor domains yet remains to be clarified. Methodology/Principal Findings: We report a detailed molecular dynamics simulation and binding energy analysis of the recognition of JMJD2A-tudor with four different histone tails. 25 ns fully unrestrained molecular dynamics simulations are carried out for each of the bound and free structures. We investigate the important hydrogen bonds and electrostatic interactions between the tudor domains and the peptide molecules and identify the critical residues that stabilize the complexes. Our binding free energy calculations show that H4K20me2 and H3K9me3 peptides have the highest and lowest affinity to JMJD2A-tudor, respectively. We also show that H4K20me2 peptide adopts the same binding mode with H4K20me3 peptide, and H3K9me3 peptide adopts the same binding mode with H3K4me3 peptide. Decomposition of the enthalpic and the entropic contributions to the binding free energies indicate that the recognition of the histone peptides is mainly driven by favourable van der Waals interactions. Residue decomposition of the binding free energies with backbone and side chain contributions as well as their energetic constituents identify the hotspots in the binding interface of the structures. Conclusion: Energetic investigations of the four complexes suggest that many of the residues involved in the interactions are common. However, we found two receptor residues that were related to selective binding of the H3 and H4 ligands. Modifications or mutations on one of these residues can selectively alter the recognition of the H3 tails or the H4 tails

The culture history of Madagascar

Madagascar's culture is a unique fusion of elements drawn from the western, northern, and eastern shores of the Indian Ocean, and its past has fascinated many scholars, yet systematic archaeological research is relatively recent on the island. The oldest traces of visitors are from the first century AD. Coastal settlements, with clear evidence of ties to the western Indian Ocean trading network, were established in several places over the next millennium. Important environmental changes of both plant and animal communities are documented over this period, including the extinctions of almost all large animal species. Urban life in Madagascar began with the establishment of the entrepôt of Mahilaka on the northwest coast of the island in the twelfth century. At about the same time, communities with ties to the trade network were established around the island's coasts. From the fourteenth to the sixteenth century, social hierarchies developed in several regions of the island. During the succeeding two centuries, Madagascar saw the development of state polities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45256/1/10963_2004_Article_BF00997802.pd