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ACKNOWLEDGMENTS We thank the HIV nurses and physicians from the two HIV clinics involved in this study (Academic Medical Center, Amsterdam; Erasmus Medical Center, Rotterdam) for their input and collaboration. We also express our gratitude to the participating patients. Finally, we thank Nicolette Strik-Mulder for her help with transcribing the audio recordings. FUNDING This study was funded by ZonMw (the Netherlands), program “Doelmatigheidsonderzoek” (grant 171002208). This funding source had no role in study design, data collection, analysis, interpretation, or writing of the report.

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The HML and HMR mating loci of Saccharomyces cerevisiae are bound in silent chromatin, which is assembled at the flanking E and I transcriptional silencers. The retrotransposon Ty5 preferentially integrates into regions of silent chromatin, and Ty5 insertions near the HMR-E silencer account for ≈2% of total transposition events. Most Ty5 insertions occur within 800 bp on either side of the autonomously replicating consensus sequence within HMR-E. Ty5 target preference is determined by silent chromatin, because integration near HMR-E is abolished in strains with silencer mutations that alleviate transcriptional repression. The recognition of specific DNA sequences per se does not direct integration, rather, it is the protein complex assembled at the silencers. As demonstrated here for Ty5, recognition of specific chromatin domains may be a general mechanism by which retrotransposons and retroviruses determine integration sites.

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