Qi Zhou

Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.Bupropion is used clinically to treat depression and to promote smoking cessation. It is metabolized by CYP2B6 to its active metabolite hydroxybupropion, yet alterations in CYP2B6 activity have little impact on bupropion plasma levels. Furthermore, less than 10% of a bupropion dose is excreted as urinary bupropion and its characterized metabolites hydroxybupropion, threohydrobupropion, and erythrohydrobupropion, suggesting that alternative metabolic pathways may exist. In vitro data suggested CYP2C19 could metabolize bupropion. The current study investigated the impact of functional CYP2C19 genetic variants on bupropion pharmacokinetics and treatment outcomes. In 42 healthy volunteers, CYP2C19∗2 was associated with higher bupropion area under the plasma concentration-time curve, but similar hydroxybupropion AUC. The mean bupropion AUC was 771 versus 670 hours·ng/ml in individuals with and without CYP2C19∗2, respectively. CYP2C19∗2 was also associated with higher threohydrobupropion and erythrohydrobupropion AUC. Adjusting for CYP2B6 genotype did not alter these associations, and CYP2C19 variants did not alter the utility of the hydroxybupropion/bupropion ratio as a measure of CYP2B6 activity. Finally, in a clinical trial of 540 smokers, CYP2C19 genotype was not associated with smoking cessation outcomes, supporting the hypothesis that bupropion response is mediated by hydroxybupropion, which is not altered by CYP2C19. In conclusion, our study reports the first in vivo evidence that reduced CYP2C19 activity significantly increases the steady-state exposure to bupropion and its reductive metabolites threohydrobupropion and erythrohydrobupropion. These pharmacokinetic changes were not associated with differences in bupropion's ability to promote smoking cessation in smokers, but may influence the side effects and toxicity associated with bupropion.

Adopting free word association test, the present study investigated the developmental features of Yi students’ Chinese mental lexicon. Eighty primary school students and 85 senior high school students in two typical Yi-Han bilingual schools in Yuexi County were recruited as the research subjects. With Yi language as their L1, all the participants started learning Chinese after entering primary school. The stimuli were 108 words selected from the 9,000 most frequently used words in modern Chinese, including 36 nouns, 36 verbs, and 36 adjectives. The responses were analyzed using the framework proposed by the responses were analyzed using a three-layer framework. The results showed that the mental lexicon of Yi primary and middle school students were mainly connected with each other by meanings, with form-based connection followed. Compared with previous studies, their phonological associations accounted for a relatively higher proportion, while semantic associations were relatively weakened. Syntagmatic associations were of primary importance, with paradigmatic and encyclopedic associations followed. While syntagmatic relation was centered on determinative and governing associations, paradigmatic relation was dominated by adjacent and reverse associations. The development rate of syntagmatic associations was faster than that of paradigmatic and encyclopedic associations; no significant improvement was found on students’ adjacent, layer, homogeneous and supplement associations from primary school to high school. The findings generate important implications for Yi students’ Chinese language education.

To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data.We recovered a highly resolved tree that confirms previously controversial sister or close relationships.We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.

The key economic issues in implementing the law of unilateral mistake are twofold. First, it should avoid misallocation of resources; second, it ought to create a sufficient incentive for acquisition of information. However, the rule of unilateral mistake in English contract law does not serve these economic goals satisfactorily. The existing law and economics literature deals extensively with how to achieve these ends by designing the legal standards for a unilateral mistake which can nullify the contract, with little discussion of the function of legal remedy. This paper offers a remedy-based approach and argues that it has economic advantages over the current law.