Brassinosteroids （BRs） are a major group of plant hormones that regulate plant growth and development. BRI1, a protein localized to the plasma membrane, functions as a BR receptor and it has been proposed that its k...Brassinosteroids （BRs） are a major group of plant hormones that regulate plant growth and development. BRI1, a protein localized to the plasma membrane, functions as a BR receptor and it has been proposed that its kinase activity has an essential role in BR-regulated plant growth and development. Here we report the isolation and molecular characterization of a new allele of bril, bril-301, which shows moderate morphological phenotypes and a reduced response to BRs under normal growth conditions. Sequence analysis identified a two-base alteration from GG to AT, resulting in a conversion of 989G to 9891 in the BRI1 kinase domain. An in vitro assay of kinase activity showed that bril-301 has no detectable autophosphorylation activity or phosphorylation activity towards the BRI1 substrates TTL and BAK1. Furthermore, our results suggest that bril-301, even with extremely impaired kinase activity, still retains partial function in regulating plant growth and development, which raises the question of whether BRI1 kinase activity is essential for BR-mediated growth and development in higher plants.展开更多
目的:探讨氟哌噻吨美利曲辛对更年期房颤合并肠易激综合征的临床治疗效果.方法:选择2011-01/2015-03广西中医药大学第一附属医院收治的女性更年期综合征发生房颤合并肠易激综合征者114例,均实施对症支持处理,精神心理治疗上,对照组使用...目的:探讨氟哌噻吨美利曲辛对更年期房颤合并肠易激综合征的临床治疗效果.方法:选择2011-01/2015-03广西中医药大学第一附属医院收治的女性更年期综合征发生房颤合并肠易激综合征者114例,均实施对症支持处理,精神心理治疗上,对照组使用氟哌噻吨,观察组则使用氟哌噻吨美利曲辛.比较两组治疗前后汉密顿抑郁量表(Hamilton Depression Scale,HAMD)和汉密顿焦虑量表(Hamilton Anxiety Scale,H A M A)评分变化,房颤发生情况及消化系症状变化,P物质(substance P,SP)和神经肽Y(neuropeptide Y,NPY)变化及治疗期间发生的不良反应情况.结果:治疗后观察组HAMD和HAMA评分低于对照组(P<0.05),心房颤动发作次数和排便次数少于对照组(P<0.05),每次持续时间和腹痛时间短于对照组(P<0.05),SP低于对照组(P<0.05),NPY高于对照组(P<0.05),发生口干、心动过速、锥体外系反应及失眠的比例显著低于对照组(P<0.05).结论:氟哌噻吨美利曲辛治疗更年期房颤合并腹泻型肠易激综合征,能显著降低患者焦虑抑郁心理,改善心律失常及消化系症状,并减少不良反应.展开更多
Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisti- cated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and mad...Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisti- cated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta （OI） that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.展开更多
The endoplasmic reticulum-associated degradation （ERAD） is a highly conserved mechanism to remove mis- folded membrane/secretory proteins from the endoplasmic reticulum （ER）. While many of the individual component...The endoplasmic reticulum-associated degradation （ERAD） is a highly conserved mechanism to remove mis- folded membrane/secretory proteins from the endoplasmic reticulum （ER）. While many of the individual components of the ERAD machinery are well characterized in yeast and mammals, our knowledge of a plant ERAD process is rather limited. Here, we report a functional study of an Arabidopsis homolog （AtOS9） of an ER luminal lectin Yos9 （OS-9 in mammals） that recognizes a unique asparagine-linked glycan on misfolded proteins. We discovered that AtOS9 is an ER-Iocalized glyco- protein that is co-expressed with many known/predicted ER chaperones. AT-DNA insertional atos9-t mutation blocks the degradation of a structurally imperfect yet biochemically competent brassinosteroid （BR） receptor bril-9, causing its increased accumulation in the ER and its consequent leakage to the cell surface responsible for restoring the BR sensitivity and suppressing the dwarfism of the bril-9 mutant. In addition, we identified a missense mutation in AtOS9 in a recently discovered ERAD mutant ems-rnutagenized bril suppressor 6 （ebs6-1）. Moreover, we showed that atos9-t also inhibits the ERAD of bril-5, another ER-retained BR receptor, and a misfolded EFR, a BRIl-like receptor for the bacterial translation elongation factor EF-Tu. Furthermore, we found that AtOS9 interacted biochemically and genetically with EBS5, an Arabidopsis homolog of the yeast Hrd3/mammalian SellL known to collaborate with Yos9/OS-9 to select ERAD clients. Taken together, our results demonstrated a functional role of AtOS9 in a plant ERAD process that degrades misfolded receptor-like kinases.展开更多
Brassinosteroids （BRs） are important plant hormones that act synergistically with auxin to regulate a variety of plant developmental and physiological processes. In the past decade, genetic and biochemical studies h...Brassinosteroids （BRs） are important plant hormones that act synergistically with auxin to regulate a variety of plant developmental and physiological processes. In the past decade, genetic and biochemical studies have revealed a linear signaling pathway that relies on protein phosphorylation to transmit the BR signal into the nucleus, altering ex- pression of hundreds of genes to promote plant growth. We conducted an activation-tagging based suppressor screen to look for Arabidopsis genes that, when overexpressed by inserted 35S enhancer elements, could suppress the dwarf phe- notype of a weak BR receptor mutant bril-301. This screen identified a total of six dominant activation-tagged bril sup- pressors （atbs-Ds）. Using a plasmid rescue approach, we discovered that the bril-301 suppression effect in four atbs-D mutants （atbs3-D to atbs6-D） was caused by overexpression of a YUCCA gene thought to be involved in tryptophan- dependent auxin biosynthesis. Interestingly, the three activation-tagged YUCCA genes belong to the YUCCA IIA subfamily that includes two other members out of 11 known Arabidopsis YUCCA genes. In addition, our molecular studies revealed a T-DNA insertion near a basic helix-loop-helix gene in atbsl-D and a T-DNA insertion in a region carrying a BR biosynthetic gene in atbs2-D. Further studies of these atbs-D mutants could lead to better understanding of the BR signaling process and the BR-auxin interaction.展开更多
The reporter introduces Xu Chaofeng the general manger of the yun Da paper making equipmentCo., Ltd. His firm and indomitable pioneering Spirit in the hard Course to set up his enterprise.
基金We thank Prof Joanne Chory （The Salk Institute for Biological Studies, USA） for providing the Arabidopsis bril-101 mutant seeds. This work was supported by grants from the National Natural Science Foundation of China （grant numbers： 30070074, 30330040 and 30570161）.
文摘Brassinosteroids （BRs） are a major group of plant hormones that regulate plant growth and development. BRI1, a protein localized to the plasma membrane, functions as a BR receptor and it has been proposed that its kinase activity has an essential role in BR-regulated plant growth and development. Here we report the isolation and molecular characterization of a new allele of bril, bril-301, which shows moderate morphological phenotypes and a reduced response to BRs under normal growth conditions. Sequence analysis identified a two-base alteration from GG to AT, resulting in a conversion of 989G to 9891 in the BRI1 kinase domain. An in vitro assay of kinase activity showed that bril-301 has no detectable autophosphorylation activity or phosphorylation activity towards the BRI1 substrates TTL and BAK1. Furthermore, our results suggest that bril-301, even with extremely impaired kinase activity, still retains partial function in regulating plant growth and development, which raises the question of whether BRI1 kinase activity is essential for BR-mediated growth and development in higher plants.
文摘目的:探讨氟哌噻吨美利曲辛对更年期房颤合并肠易激综合征的临床治疗效果.方法:选择2011-01/2015-03广西中医药大学第一附属医院收治的女性更年期综合征发生房颤合并肠易激综合征者114例,均实施对症支持处理,精神心理治疗上,对照组使用氟哌噻吨,观察组则使用氟哌噻吨美利曲辛.比较两组治疗前后汉密顿抑郁量表(Hamilton Depression Scale,HAMD)和汉密顿焦虑量表(Hamilton Anxiety Scale,H A M A)评分变化,房颤发生情况及消化系症状变化,P物质(substance P,SP)和神经肽Y(neuropeptide Y,NPY)变化及治疗期间发生的不良反应情况.结果:治疗后观察组HAMD和HAMA评分低于对照组(P<0.05),心房颤动发作次数和排便次数少于对照组(P<0.05),每次持续时间和腹痛时间短于对照组(P<0.05),SP低于对照组(P<0.05),NPY高于对照组(P<0.05),发生口干、心动过速、锥体外系反应及失眠的比例显著低于对照组(P<0.05).结论:氟哌噻吨美利曲辛治疗更年期房颤合并腹泻型肠易激综合征,能显著降低患者焦虑抑郁心理,改善心律失常及消化系症状,并减少不良反应.
文摘Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisti- cated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta （OI） that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.
基金This work was partly supported by grants from National Institutes of Health （GM060519） and National Science Foundation （IOS 1121496） to J.L.
文摘The endoplasmic reticulum-associated degradation （ERAD） is a highly conserved mechanism to remove mis- folded membrane/secretory proteins from the endoplasmic reticulum （ER）. While many of the individual components of the ERAD machinery are well characterized in yeast and mammals, our knowledge of a plant ERAD process is rather limited. Here, we report a functional study of an Arabidopsis homolog （AtOS9） of an ER luminal lectin Yos9 （OS-9 in mammals） that recognizes a unique asparagine-linked glycan on misfolded proteins. We discovered that AtOS9 is an ER-Iocalized glyco- protein that is co-expressed with many known/predicted ER chaperones. AT-DNA insertional atos9-t mutation blocks the degradation of a structurally imperfect yet biochemically competent brassinosteroid （BR） receptor bril-9, causing its increased accumulation in the ER and its consequent leakage to the cell surface responsible for restoring the BR sensitivity and suppressing the dwarfism of the bril-9 mutant. In addition, we identified a missense mutation in AtOS9 in a recently discovered ERAD mutant ems-rnutagenized bril suppressor 6 （ebs6-1）. Moreover, we showed that atos9-t also inhibits the ERAD of bril-5, another ER-retained BR receptor, and a misfolded EFR, a BRIl-like receptor for the bacterial translation elongation factor EF-Tu. Furthermore, we found that AtOS9 interacted biochemically and genetically with EBS5, an Arabidopsis homolog of the yeast Hrd3/mammalian SellL known to collaborate with Yos9/OS-9 to select ERAD clients. Taken together, our results demonstrated a functional role of AtOS9 in a plant ERAD process that degrades misfolded receptor-like kinases.
文摘Brassinosteroids （BRs） are important plant hormones that act synergistically with auxin to regulate a variety of plant developmental and physiological processes. In the past decade, genetic and biochemical studies have revealed a linear signaling pathway that relies on protein phosphorylation to transmit the BR signal into the nucleus, altering ex- pression of hundreds of genes to promote plant growth. We conducted an activation-tagging based suppressor screen to look for Arabidopsis genes that, when overexpressed by inserted 35S enhancer elements, could suppress the dwarf phe- notype of a weak BR receptor mutant bril-301. This screen identified a total of six dominant activation-tagged bril sup- pressors （atbs-Ds）. Using a plasmid rescue approach, we discovered that the bril-301 suppression effect in four atbs-D mutants （atbs3-D to atbs6-D） was caused by overexpression of a YUCCA gene thought to be involved in tryptophan- dependent auxin biosynthesis. Interestingly, the three activation-tagged YUCCA genes belong to the YUCCA IIA subfamily that includes two other members out of 11 known Arabidopsis YUCCA genes. In addition, our molecular studies revealed a T-DNA insertion near a basic helix-loop-helix gene in atbsl-D and a T-DNA insertion in a region carrying a BR biosynthetic gene in atbs2-D. Further studies of these atbs-D mutants could lead to better understanding of the BR signaling process and the BR-auxin interaction.
文摘The reporter introduces Xu Chaofeng the general manger of the yun Da paper making equipmentCo., Ltd. His firm and indomitable pioneering Spirit in the hard Course to set up his enterprise.
