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41.
Hai-Bing He Li-Xin Gao Qi-Feng Deng Wei-Ping Ma Chun-Lan Tang Wen-Wei Qiu Jie Tang Jing-Ya Li Jia Li Fan Yang 《Bioorganic & medicinal chemistry letters》2012,22(23):7237-7242
Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of both insulin and leptin signals. For years, inhibiting of PTP1B has been considered to be a potential therapeutics for treating Type 2 diabetes and obesity. Recently, we recognized lithocholic acid (LCA) as a natural inhibitor against PTP1B (IC50 = 12.74 μM) by a vertical screen for the first time. Further SAR research was carried out by synthesizing and evaluating a series of compounds bearing two methyls at C-4 position and a fused heterocycle to ring A. Among them, compound 14b achieved a PTP1B inhibitory activity about eightfold than LCA and a 14-fold selectivity over the homogenous enzyme TCPTP. 相似文献
42.
镉胁迫对家蚕脂肪体脂质过氧化物含量及抗氧化酶活性和mRNA表达的影响 总被引:2,自引:0,他引:2
【目的】探讨鳞翅目模式昆虫家蚕Bombyx mori作为重金属污染的监测指示生物在镉胁迫下的酶反应及相关的基因表达。【方法】给家蚕幼虫期全龄添食镉(Cd2+), 调查不同性别家蚕5龄幼虫脂肪体中脂质过氧化物丙二醛(MDA)的含量, 超氧化物歧化酶(SOD)、 过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的活性及其基因表达水平的变化。【结果】Cd2+胁迫对雌雄家蚕MDA 含量均具有浓度效应关系, MDA含量随Cd2+胁迫浓度的升高而增加。Cd2+胁迫下, SOD和CAT活性表现为先升后降的变化趋势, Pearson相关性分析显示SOD和CAT活性变化有显著相关性(雄: R=0.770, P=0.001; 雌: R=0.854, P=0.000)。雌性家蚕脂肪体中CAT活性变化和Cat mRNA水平的表达具有正相关性(R=0.712, P=0.003)。雄性家蚕脂肪体中GSH-Px活性随Cd2+胁迫浓度的升高而增加, 显示浓度 效应关系, 12.5~50 mg/kg Cd2+胁迫组GSH-Px活性与对照相比有显著差异(P<0.05), 其活性和GSH-Px mRNA水平的表达具有正相关性(R=0.834, P=0.000); 雌性家蚕脂肪体中GSH-Px活性表现为先升后降的变化趋势, 12.5 mg/kg Cd2+胁迫组GSH-Px活性与对照相比有显著增加(P<0.01)。【结论】结果表明, 急性镉胁迫对家蚕脂肪体有明显的毒性作用, 其作用机制与脂质过氧化加剧和抗氧化酶活性变化有关。家蚕对重金属镉的解毒机制有性别相关性。 相似文献
43.
The calpains are a family of cysteine proteases with closely related amino acid sequences, but a wide range of Ca(2+) requirements (K(d)). For m-calpain, K(d) is approximately 325microM, for mu-calpain it is approximately 50microM, and for calpain 3 it is not strictly known but may be approximately 0.1microM. On the basis of previous structure determination of m-calpain we postulated that two regions of the calpain large subunits, the N-terminal peptide (residues 1-20) and a domain III-IV linker peptide (residues 514-530 in m-calpain) were important in defining K(d). The mutations Lys10Thr in the N-terminal peptide, and Glu517Pro in the domain linker peptide, reduced K(d) of m-calpain by 30% and 42%, respectively, revealing that these two regions are functionally important. The increased Ca(2+)-sensitivity of these mutants demonstrate that the Lys10-Asp148 salt link and the short beta-sheet interaction involving Glu517 are factors contributing to the high K(d) of m-calpain. Though these two regions are physically remote from the active site and Ca(2+)-binding site, they play significant roles in regulating the response of calpain to Ca(2+). Differences in these interactions in mu-calpain and in calpain 3 are also consistent with their progressively lower K(d) values. 相似文献
44.
Qiu YC Zhou RH Kong XY Zhang SS Jia JZ 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(8):1524-1531
A powdery mildew resistance gene from Triticum urartu Tum. accession UR206 was successfully transferred into hexaploid wheat (Triticum aestivum L.) through crossing and backcrossing. The F1 plants, which had 28 chromosomes and an average of 5.32 bivalents and 17.36 univalents in meiotic pollen mother cells (PMC),
were obtained through embryos rescued owing to shriveling of endosperm in hybrid seed of cross Chinese Spring (CS) × UR206.
Hybrid seeds were produced through backcrossing F1 with common wheat parents. The derivative lines had normal chromosome numbers and powdery mildew resistance similar to the
donor UR206, indicating that the powdery mildew resistance gene originating from T. urartu accession UR206 was successfully transferred and expressed in a hexaploid wheat background. Genetic analysis indicated that
a single dominant gene controlled the powdery mildew resistance at the seedling stage. To map and tag the powdery mildew resistance
gene, 143 F2 individuals derived from a cross UR206 × UR203 were used to construct a linkage map. The resistant gene was mapped on the
chromosome 7AL based on the mapped microsatellite makers. The map spanned 52.1 cM and the order of these microsatellite loci
agreed well with the established microsatellite map of chromosome arm 7AL. The resistance gene was flanked by the microsatellite
loci Xwmc273 and Xpsp3003, with the genetic distances of 2.2 cM and 3.8 cM, respectively. On the basis of the origin and chromosomal location of the
gene, it was temporarily designated PmU. 相似文献
45.
遥感数据支持下不同地表覆盖的区域蒸散 总被引:11,自引:0,他引:11
将地表能量平衡系统(SEBS)扩展成遥感日蒸散估算模型,利用MODIS遥感数据估算了黄淮海地区的区域蒸散,并在地理信息系统的支持下分析了不同地表覆盖下的区域蒸散统计分布特征.在缺乏各地表覆盖类型相应蒸散量实测值进行对比的情况下,以2001年4月17日估算的日蒸散量为例,通过各地表覆盖类型日蒸散量间的相互对比分析表明,SEBS估算的区域日蒸散量具有一定的合理性.分析结果表明:在黄淮海地区,荒地具有最低的蒸散量;森林、灌木、草地等地表覆盖类型具有中等的蒸散量;而水体、湿地以及耕地具有较高的蒸散量.可能由于包含绿地和水面,城镇用地的蒸散量也较高.土壤含水量的空间差异性导致森林、灌木、草地和耕地等地表覆盖类型的蒸散量具有明显的空间差异性.耕地蒸散量的空间差异性可以为制定合理、高效的农田灌溉计划提供指示作用.SEBS遥感日蒸散模型的局限性在于有可能低估水体和湿地等地表覆盖类型的蒸散量. 相似文献
46.
47.
An inhibitor-tolerance strain, Bacillus coagulans GKN316, was developed through atmospheric and room temperature plasma (ARTP) mutation and evolution experiment in condensed dilute-acid hydrolysate (CDH) of corn stover. The fermentabilities of other hydrolysates with B. coagulans GKN316 and the parental strain B. coagulans NL01 were assessed. When using condensed acid-catalyzed steam-exploded hydrolysate (CASEH), condensed acid-catalyzed liquid hot water hydrolysate (CALH) and condensed acid-catalyzed sulfite hydrolysate (CASH) as substrates, the concentration of lactic acid reached 45.39, 16.83, and 18.71 g/L by B. coagulans GKN316, respectively. But for B. coagulans NL01, only CASEH could be directly fermented to produce 15.47 g/L lactic acid. The individual inhibitory effect of furfural, 5-hydroxymethylfurfural (HMF), vanillin, syringaldehyde and p-hydroxybenzaldehyde (pHBal) on xylose utilization by B. coagulans GKN316 was also studied. The strain B. coagulans GKN316 could effectively convert these toxic inhibitors to the less toxic corresponding alcohols in situ. These results suggested that B. coagulans GKN316 was well suited to production of lactic acid from undetoxified lignocellulosic hydrolysates. 相似文献
48.
49.
The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects. 相似文献
50.
Genome-wide association studies (GWAS) have rapidly become a powerful tool in genetic studies of complex diseases and traits. Traditionally, single marker-based tests have been used prevalently in GWAS and have uncovered tens of thousands of disease-associated SNPs. Network-assisted analysis (NAA) of GWAS data is an emerging area in which network-related approaches are developed and utilized to perform advanced analyses of GWAS data in order to study various human diseases or traits. Progress has been made in both methodology development and applications of NAA in GWAS data, and it has already been demonstrated that NAA results may enhance our interpretation and prioritization of candidate genes and markers. Inspired by the strong interest in and high demand for advanced GWAS data analysis, in this review article, we discuss the methodologies and strategies that have been reported for the NAA of GWAS data. Many NAA approaches search for subnetworks and assess the combined effects of multiple genes participating in the resultant subnetworks through a gene set analysis. With no restriction to pre-defined canonical pathways, NAA has the advantage of defining subnetworks with the guidance of the GWAS data under investigation. In addition, some NAA methods prioritize genes from GWAS data based on their interconnections in the reference network. Here, we summarize NAA applications to various diseases and discuss the available options and potential caveats related to their practical usage. Additionally, we provide perspectives regarding this rapidly growing research area. 相似文献