Genome Re-Sequencing of Diverse Sweet Cherry (Prunus avium) Individuals Reveals a Modifier Gene Mutation Conferring Pollen-Part Self-Compatibility.

The S-RNase-based gametophytic self-incompatibility (GSI) reproduction barrier is important for maintaining genetic diversity in species of the families Solanaceae, Plantaginaceae and Rosaceae. Among the plant taxa with S-RNase-based GSI, Prunus species in the family Rosaceae exhibit Prunus-specific self-incompatibility (SI). Although pistil S and pollen S determinants have been identified, the mechanism underlying SI remains uncharacterized in Prunus species. A putative pollen-part modifier was identified in this study. Disruption of this modifier supposedly confers self-compatibility (SC) to sweet cherry (Prunus avium) 'Cristobalina'. To identify the modifier, genome re-sequencing experiments were completed involving sweet cherry individuals from 18 cultivars and 43 individuals in two segregating populations. Cataloging of subsequences (35 bp kmers) from the obtained genomic reads, while referring to the mRNA sequencing data, enabled the identification of a candidate gene [M locus-encoded GST (MGST)]. Additionally, the insertion of a transposon-like sequence in the putative MGST promoter region in 'Cristobalina' down-regulated MGST expression levels, probably leading to the SC of this cultivar. Phylogenetic, evolutionary and gene expression analyses revealed that MGST may have undergone lineage-specific evolution, and the encoded protein may function differently from the corresponding proteins encoded by GST orthologs in other species, including members of the subfamily Maloideae (Rosaceae). Thus, MGST may be important for Prunus-specific SI. The identification of this novel modifier will expand our understanding of the Prunus-specific GSI system. We herein discuss the possible functions of MGST in the Prunus-specific GSI system.

The recovery time-course of CYP3A after induction by St John's wort administration.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: St John's wort causes the induction of CYP3A. Little is known about how long the effect remains after cessation of St John's wort. WHAT THIS STUDY ADDS: The in vivo CYP3A activity returns progressively to the basal level approximately 1 week after cessation of St John's wort administration AIMS: To examine the recovery time course of CYP3A after enzyme induction by St John's wort administration. METHODS: The subjects were 12 healthy men, aged 20-33 years. On the first day, they received an oral dose of midazolam 5 mg without St John's wort (day -14). From the next day, they took St John's wort for 14 days. On the last day of St John's wort treatment (day 0) and 3 and 7 days after completion of St John's wort treatment (days 3 and 7), they received the same dose of midazolam. On each day, blood samples were obtained until 8 h after midazolam administration. Plasma concentrations of midazolam were measured by HPLC. Pharmacokinetic parameters of midazolam were determined using noncompartmental analysis. RESULTS: Apparent oral clearance of midazolam was significantly increased after St John's wort administration from 65.3 +/- 8.4 l h(-1) (day -14) to 86.8 +/- 17.3 l h(-1) (day 0). It returned to the control level 7 days after the completion of St John's wort (day 7, 59.7 +/- 3.8 l h(-1)). No significant difference in the elimination half-life between the four periods of the study was observed. The changes in apparent oral clearance after St John's wort discontinuation indicated that CYP3A activity recovers from enzyme induction with an estimated half-life of 46.2 h. CONCLUSIONS: CYP3A activity induced by St John's wort administration progressively returns to the basal level after approximately 1 week. This finding may provide useful information to avoid clinically significant interactions of St John's wort with CYP3A substrates.

Effect of St. John's wort on the pharmacokinetics of theophylline in healthy volunteers.

The objective of this study was to investigate the effect of St. John's wort (SJW, Hypericum perforatum) on the pharmacokinetics of theophylline in healthy volunteers. Twelve healthy Japanese male volunteers participated in this randomized, open-labeled, crossover study. The subjects took an SJW caplet (300 mg) three times a day for 15 days. On day 14, they received a single oral dose of 400 mg of theophylline. They took the same dose of theophylline without SJW treatment on another occasion. Plasma and urine samples were obtained during a 48-hour period after theophylline administration. Theophylline concentrations in plasma and urine, as well as the major metabolites (13U, 1U, 3X) in urine, were measured. SJW caused no significant changes in the pharmacokinetics of theophylline in plasma. SJW administration tended to increase the ratio of 1U/the total amount excreted in urine. However, no changes in the ratio of unchanged theophylline, 13U, and 3X were observed. It is unlikely that the effect of 15 days of treatment with SJW on CYPs is sufficient to cause a change in plasma theophylline concentrations.