The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1–Nrf2 protein–protein interaction(PPI) has become an important drug target to upregul...The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1–Nrf2 protein–protein interaction(PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1–Nrf2PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1's cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1–Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1–Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.展开更多
Breeding high-yielding and nutrient-efficient cultivars is one strategy to simultaneously resolve the problems of food security,resource shortage,and environmental pollution.However,the potential increased yield and r...Breeding high-yielding and nutrient-efficient cultivars is one strategy to simultaneously resolve the problems of food security,resource shortage,and environmental pollution.However,the potential increased yield and reduction in fertilizer input achievable by using high-yielding and nutrient-efficient cultivars is unclear.In the present study,we evaluated the yield and nitrogen use efficiency(NUE) of 40 commercial maize hybrids at five locations in North and Northeast China in 2008 and 2009.The effect of interaction between genotype and nitrogen(N) input on maize yield was significant when the yield reduction under low-N treatment was 25%-60%.Based on the average yields achieved with high or low N application,the tested cultivars were classified into four types based on their NUE:efficient-efficient(EE) were efficient under both low and high N inputs,high-N efficient(HNE) under only high N input,low-N efficient(LNE) under only low N input,and nonefficient-nonefficient under neither low nor high N inputs.Under high N application,EE and HNE cultivars could potentially increase maize yield by 8%-10% and reduce N input by 16%-21%.Under low N application,LNE cultivars could potentially increase maize yield by 12%.We concluded that breeding for N-efficient cultivars is a feasible strategy to increase maize yield and/or reduce N input.展开更多
A plant＇s capability to cope with environmental challenges largely relies on signal transmission through mitogen-activated protein kinase （MAPK） cascades. In Arabidopsis thaliana, MPK3 is particularly strongly asso...A plant＇s capability to cope with environmental challenges largely relies on signal transmission through mitogen-activated protein kinase （MAPK） cascades. In Arabidopsis thaliana, MPK3 is particularly strongly associated with numerous abiotic and biotic stress responses. Identification of MPK3 substrates is a milestone towards improving stress resistance in plants. Here, we characterize AZI1, a lipid transfer protein （LTP）-related hybrid proline-rich protein （HyPRP）, as a novel target of MPK3. AZI1 is phosphorylated by MPK3 in vitro. As documented by co-immunoprecipitation and bimolecular fluorescence complementation experiments, AZI1 interacts with MPK3 to form protein complexes in planta. Furthermore, null mutants of azil are hypersensitive to salt stress, while AZIl-overexpressing lines are markedly more tolerant. AZI1 overexpression in the mpk3 genetic background partially alleviates the salt-hypersensitive phenotype of this mutant, but functional MPK3 appears to be required for the full extent of AZIl-conferred robustness. Notably, this robustness does not come at the expense of normal development. Immunoblot and RT-PCR data point to a role of MPK3 as positive regulator of AZI1 abundance.展开更多
Owing to the complexity of the pipe-in-pipe (PIP) riser system in structure, load and restraint, many problems arise in the structural analysis of the system. This paper presents a new method for nonlinear static fini...Owing to the complexity of the pipe-in-pipe (PIP) riser system in structure, load and restraint, many problems arise in the structural analysis of the system. This paper presents a new method for nonlinear static finite element stress analysis of the PIP riser system. The finite element (FE) model of the PIP riser system is built via software AutoPIPE 6.1. According to the specialties of a variety of components in the PIP riser system, different elements are used so as to model the system accurately. Allowing for the complication in modeling the effects of seabed restraint, a technique based on the bilinear spring concept is developed to calculate the soil properties. Then, based on a pipeline project, the entire procedure of stress analysis is discussed in detail, including creation of an FE model, processing of input data and analysis of results. A wide range of loading schemes is investigated to ascertain that the stresses remain within the acceptable range of the pipe material strength. Finally, the effects of the location of flanges, the thermal expansion of submarine pipelines and the seabed restraint on stress distribution in the riser and expansion loop are studied, which are valuable for pipeline designers.展开更多
Wheat(Triticum aestivum L.) is one of the three major global food crops. Hightemperature stress can affect its yield and quality. Studies of the effect of hightemperature stress on wheat kernel development are importa...Wheat(Triticum aestivum L.) is one of the three major global food crops. Hightemperature stress can affect its yield and quality. Studies of the effect of hightemperature stress on wheat kernel development are important because they can reveal the stability of wheat quality and lead to the genetic improvement of wheat quality traits. In this study, the isobaric tags for relative and absolute quantitation(iTRAQ)method was adopted to analyze changes in the protein expression profile of wheat cultivars under high temperature stress. The protein content of wheat grain increased under heat stress, while the SDS-sedimentation value and starch content decreased.Grain filling was deficient under high temperature stress, which reduced thousandkernel weight but did not affect wheat kernel length. The 207 differentially expressed proteins identified in Gaocheng 8901 under heat stress were associated with energy metabolism, growth and development, and stress response. Gene Ontology enrichment analysis showed that the annotated proteins that were differentially expressed in Gaocheng 8901 under heat stress were involved mainly in stimulus response, abiotic stress response, stress response, and plasma membrane. A set of 78 differentially expressed proteins were assigned to 83 KEGG signaling/metabolic pathways. KEGG pathway enrichment analysis showed that this set of proteins was significantly enriched in members of 51 pathways, and the proteins participated mainly in protein synthesis in the endoplasmic reticulum, starch and sucrose metabolism, and reaction on ribosomes. Five differentially expressed proteins were involved in protein–protein interaction networks that may greatly influence the yield and quality of wheat grain. In wheat, high-temperature stress leads to a variety of effects on protein expression and may ultimately cause changes in yield and quality.展开更多
基金the financial support of Grants CA133791, CA125868, and MH093197 from the National Institutes of Health, United States
文摘The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1–Nrf2 protein–protein interaction(PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1–Nrf2PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1's cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1–Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1–Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.
基金supported by the National Basic Research Program of China (2011CB100305,2009CB11860)the National Natural Science Foundation of China (31121062,31172015)the Special Fund for Agriculture Profession (201103003)
文摘Breeding high-yielding and nutrient-efficient cultivars is one strategy to simultaneously resolve the problems of food security,resource shortage,and environmental pollution.However,the potential increased yield and reduction in fertilizer input achievable by using high-yielding and nutrient-efficient cultivars is unclear.In the present study,we evaluated the yield and nitrogen use efficiency(NUE) of 40 commercial maize hybrids at five locations in North and Northeast China in 2008 and 2009.The effect of interaction between genotype and nitrogen(N) input on maize yield was significant when the yield reduction under low-N treatment was 25%-60%.Based on the average yields achieved with high or low N application,the tested cultivars were classified into four types based on their NUE:efficient-efficient(EE) were efficient under both low and high N inputs,high-N efficient(HNE) under only high N input,low-N efficient(LNE) under only low N input,and nonefficient-nonefficient under neither low nor high N inputs.Under high N application,EE and HNE cultivars could potentially increase maize yield by 8%-10% and reduce N input by 16%-21%.Under low N application,LNE cultivars could potentially increase maize yield by 12%.We concluded that breeding for N-efficient cultivars is a feasible strategy to increase maize yield and/or reduce N input.
文摘A plant＇s capability to cope with environmental challenges largely relies on signal transmission through mitogen-activated protein kinase （MAPK） cascades. In Arabidopsis thaliana, MPK3 is particularly strongly associated with numerous abiotic and biotic stress responses. Identification of MPK3 substrates is a milestone towards improving stress resistance in plants. Here, we characterize AZI1, a lipid transfer protein （LTP）-related hybrid proline-rich protein （HyPRP）, as a novel target of MPK3. AZI1 is phosphorylated by MPK3 in vitro. As documented by co-immunoprecipitation and bimolecular fluorescence complementation experiments, AZI1 interacts with MPK3 to form protein complexes in planta. Furthermore, null mutants of azil are hypersensitive to salt stress, while AZIl-overexpressing lines are markedly more tolerant. AZI1 overexpression in the mpk3 genetic background partially alleviates the salt-hypersensitive phenotype of this mutant, but functional MPK3 appears to be required for the full extent of AZIl-conferred robustness. Notably, this robustness does not come at the expense of normal development. Immunoblot and RT-PCR data point to a role of MPK3 as positive regulator of AZI1 abundance.
文摘Owing to the complexity of the pipe-in-pipe (PIP) riser system in structure, load and restraint, many problems arise in the structural analysis of the system. This paper presents a new method for nonlinear static finite element stress analysis of the PIP riser system. The finite element (FE) model of the PIP riser system is built via software AutoPIPE 6.1. According to the specialties of a variety of components in the PIP riser system, different elements are used so as to model the system accurately. Allowing for the complication in modeling the effects of seabed restraint, a technique based on the bilinear spring concept is developed to calculate the soil properties. Then, based on a pipeline project, the entire procedure of stress analysis is discussed in detail, including creation of an FE model, processing of input data and analysis of results. A wide range of loading schemes is investigated to ascertain that the stresses remain within the acceptable range of the pipe material strength. Finally, the effects of the location of flanges, the thermal expansion of submarine pipelines and the seabed restraint on stress distribution in the riser and expansion loop are studied, which are valuable for pipeline designers.
基金supported by the National Key Research and Development Program of China(2016YFD0100502)
文摘Wheat(Triticum aestivum L.) is one of the three major global food crops. Hightemperature stress can affect its yield and quality. Studies of the effect of hightemperature stress on wheat kernel development are important because they can reveal the stability of wheat quality and lead to the genetic improvement of wheat quality traits. In this study, the isobaric tags for relative and absolute quantitation(iTRAQ)method was adopted to analyze changes in the protein expression profile of wheat cultivars under high temperature stress. The protein content of wheat grain increased under heat stress, while the SDS-sedimentation value and starch content decreased.Grain filling was deficient under high temperature stress, which reduced thousandkernel weight but did not affect wheat kernel length. The 207 differentially expressed proteins identified in Gaocheng 8901 under heat stress were associated with energy metabolism, growth and development, and stress response. Gene Ontology enrichment analysis showed that the annotated proteins that were differentially expressed in Gaocheng 8901 under heat stress were involved mainly in stimulus response, abiotic stress response, stress response, and plasma membrane. A set of 78 differentially expressed proteins were assigned to 83 KEGG signaling/metabolic pathways. KEGG pathway enrichment analysis showed that this set of proteins was significantly enriched in members of 51 pathways, and the proteins participated mainly in protein synthesis in the endoplasmic reticulum, starch and sucrose metabolism, and reaction on ribosomes. Five differentially expressed proteins were involved in protein–protein interaction networks that may greatly influence the yield and quality of wheat grain. In wheat, high-temperature stress leads to a variety of effects on protein expression and may ultimately cause changes in yield and quality.
