Terrestrial plants must cope with drought stress to survive. Under drought stress, plants accumulate the phytohormone abscisic acid （ABA） by increasing its biosynthesis and decreasing its catabolism. However, the re...Terrestrial plants must cope with drought stress to survive. Under drought stress, plants accumulate the phytohormone abscisic acid （ABA） by increasing its biosynthesis and decreasing its catabolism. However, the regulatory pathways controlling ABA catabolism in response to drought remain largely unclear. Here, we report that the flowering repressor SHORT VEGETATIVE PHASE （SVP） is induced by drought stress and associates with the promoter regions of the ABA catabolism pathway genes CYP707A 1, CYP707A3 and AtBG1, causing decreased expression of CYP7OTA 1 and CYP707A3 but enhanced expression ofAtBG1 inArabidopsis leaves. Loss-of-function mutations in CYP707A 1 and CYP707A3 or overexpression of AtBG1 could rescue the drought-hypersensitive phenotype of svp mutant plants by increasing cellular ABA levels. Collectively, our results suggest that SVP is a central regulator of ABA catabolism and that a regulatory pathway involving SVP, CYP707A1/3, and AtBG1 plays a critical role in plant response to water deficit and plant drought resistance.展开更多
The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter...The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.展开更多
文摘Terrestrial plants must cope with drought stress to survive. Under drought stress, plants accumulate the phytohormone abscisic acid （ABA） by increasing its biosynthesis and decreasing its catabolism. However, the regulatory pathways controlling ABA catabolism in response to drought remain largely unclear. Here, we report that the flowering repressor SHORT VEGETATIVE PHASE （SVP） is induced by drought stress and associates with the promoter regions of the ABA catabolism pathway genes CYP707A 1, CYP707A3 and AtBG1, causing decreased expression of CYP7OTA 1 and CYP707A3 but enhanced expression ofAtBG1 inArabidopsis leaves. Loss-of-function mutations in CYP707A 1 and CYP707A3 or overexpression of AtBG1 could rescue the drought-hypersensitive phenotype of svp mutant plants by increasing cellular ABA levels. Collectively, our results suggest that SVP is a central regulator of ABA catabolism and that a regulatory pathway involving SVP, CYP707A1/3, and AtBG1 plays a critical role in plant response to water deficit and plant drought resistance.
文摘The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.
