排序方式: 共有100条查询结果,搜索用时 328 毫秒
61.
Sawyer JS Beight DW Britt KS Anderson BD Campbell RM Goodson T Herron DK Li HY McMillen WT Mort N Parsons S Smith EC Wagner JR Yan L Zhang F Yingling JM 《Bioorganic & medicinal chemistry letters》2004,14(13):3581-3584
We have expanded our previously reported series of pyrazole-based inhibitors of the TGF-beta type I receptor kinase domain (TbetaR-I) to now include new 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole analogues. Limited examination of the SAR of this new series in both enzyme and cell based in vitro assays has revealed selectivity differences with respect to p38 MAP kinase (p38 MAPK) depending on the nature of the 'warhead' group on the dihydropyrrolopyrazole ring. As with our original pyrazole series, phenyl substituents tended to show greater selectivity against p38 MAPK than those comprised of the quinoline-4-yl moiety. We have also achieved co-crystallization and X-ray analysis of compounds 3 and 15, two potent examples of this new series, with the TbetaR-I receptor kinase domain. 相似文献
62.
Search for haplotype interactions that influence susceptibility to type 1 diabetes, through use of unphased genotype data
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Zhang J Liang F Dassen WR Veldman BA Doevendans PA De Gunst M 《American journal of human genetics》2003,73(6):1385-1401
Type 1 diabetes is a T-cell-mediated chronic disease characterized by the autoimmune destruction of pancreatic insulin-producing beta cells and complete insulin deficiency. It is the result of a complex interrelation of genetic and environmental factors, most of which have yet to be identified. Simultaneous identification of these genetic factors, through use of unphased genotype data, has received increasing attention in the past few years. Several approaches have been described, such as the modified transmission/disequilibrium test procedure, the conditional extended transmission/disequilibrium test, and the stepwise logistic-regression procedure. These approaches are limited either by being restricted to family data or by ignoring so-called "haplotype interactions" between alleles. To overcome this limit, the present study provides a general method to identify, on the basis of unphased genotype data, the haplotype blocks that interact to define the risk for a complex disease. The principle underpinning the proposal is minimal entropy. The performance of our procedure is illustrated for both simulated and real data. In particular, for a set of Dutch type 1 diabetes data, our procedure suggests some novel evidence of the interactions between and within haplotype blocks that are across chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 11, 12, 15, 16, 17, 19, and 21. The results demonstrate that, by considering interactions between potential disease haplotype blocks, we may succeed in identifying disease-predisposing genetic variants that might otherwise have remained undetected. 相似文献
63.
Structural evolution of an enzyme specificity. The structure of rat carboxypeptidase A2 at 1.9-A resolution. 总被引:1,自引:0,他引:1
Z Faming B Kobe C B Stewart W J Rutter E J Goldsmith 《The Journal of biological chemistry》1991,266(36):24606-24612
The structure of rat carboxypeptidase A2 (CPA2), which has a unique specificity for tryptophan-containing COOH-terminal peptides, has been determined in an unliganded state at 1.9-A resolution and refined to a crystallographic R-factor of 18.3%. Comparison of the structure of CPA2 with that of bovine carboxypeptidase A (referred to here as CPA1) reveals that the specificity of the former for larger amino acids probably arises from two amino acid replacements within the binding cavity (Thr268----Ala and Leu203----Met), coupled with differences in the positions of conserved residues in a surface loop on one face of the specificity pocket. The position of the reactive-site surface loop may be affected also by a disulfide bridge between Cys210 and Cys244. In this unliganded form of the enzyme, Tyr248 takes up a position interior to the specificity pocket and is distinct from that observed in bovine CPA1. The structural differences between CPA1 and CPA2 correlate strongly with crystallographically determined temperature factors and thus appear to be largest where the enzyme is flexible. 相似文献
64.
腰痛(low back pain,LBP)是影响人类健康的最常见疾病之一,患病率高且治愈率低下。其发病机制尚不清楚,可能与多种因素有关,如椎间盘退变、关节突关节损伤、肌肉筋膜炎症等。建立恰当的动物模型有助于研究和了解LBP的发病机制、探索预防及治疗方法。本文就可诱发腰痛的动物模型研究进展综述如下。 相似文献
65.
猕猴桃溃疡病抗性育种研究进展 总被引:2,自引:0,他引:2
猕猴桃细菌性溃疡病是一种危害世界猕猴桃生产的毁灭性病害,目前尚未有有效的防治办法。培育抗性品种是保证猕猴桃产业健康发展的重要途径之一,猕猴桃溃疡病抗性育种成为近年来猕猴桃研究的热点。但是,目前大部分猕猴桃种质资源对溃疡病的抗性不明,限制了猕猴桃优异抗性种质资源的发掘和利用。虽然人们发展出了一些猕猴桃溃疡病抗性鉴定和评价方法,但是使用效果并不理想,存在较大的局限性,鉴定的准确性和稳定性还有待提高。该文针对猕猴桃溃疡病抗性育种中的几个方面,如抗性材料的选育(现有品种的抗性、抗性砧木研究和野生抗溃资源等),抗性鉴定和评价技术(大田鉴定、活体或离体鉴定等)及抗性机理研究等进行综述,并针对存在的问题,提出建设性意见。在猕猴桃溃疡病抗性育种过程中,最关键的是要建立一个科学、系统的溃疡病抗性评价体系,以对猕猴桃种质资源进行大规模的抗性普查和评估,在此基础上充分利用种间杂交和工程育种技术加快抗性育种进程,并以此带动猕猴桃溃疡病抗性机理的深入研究和抗病基因的挖掘和利用等,旨在从根本上解决猕猴桃生产中受溃疡病困扰这一关键难题,促进猕猴桃产业绿色、健康和可持续性发展。 相似文献
66.
Manynooch Faming 《The Australian journal of anthropology》2019,30(2):212-227
Idealistically speaking, schools are engines for upward social mobility. Education for ethnic minorities in Laos was set up to achieve nationalist, political, economic and sociocultural goals of ‘equity’ and ‘equality’. It was hoped that education would shift ethnic minorities from a lifestyle based on superstitious beliefs to a modern one, so that they could participate and enjoy ‘equality’ through educational equity. The purpose of this paper is to provide a case study of how equality as a promise in education has impacted on students’ upward mobility, particularly the political discourse of the ‘big man’. This paper explores social mobility provided by national education for ethnic minorities through boarding schooling. It finds that such education has yet to reposition ethnic minorities into the ethnic Lao sociocultural hierarchy. As a result, regardless of their educational success, students are still ranked as ‘ethnic minorities’ and as being ‘poor’ in the eyes of urban students, middle class and rich students, and the ethnic Lao elite. 相似文献
67.
Shipeng Li Lei Chen Liwu Zhang Xi Li Ying Liu Zhikun Wu Faming Dong Lili Wan Kede Liu Dengfeng Hong Guangsheng Yang 《Plant physiology》2015,169(4):2744-2760
68.
Faming Tian Theodora M. Mauro Zhengxiao Li 《Journal of cellular and molecular medicine》2019,23(9):5876-5883
Psoriasis (PsO) is a chronic inflammatory skin disease with both local and systemic components. PsO‐associated arthritis, known as psoriatic arthritis (PsA), develops in approximately 13%‐25% of PsO patients. Various factors associated with both PsO and PsA indicate that these conditions are part of a single disease. Identification of novel targets for the development of drugs to treat both PsO and PsA is desirable to provide more patient‐friendly treatment regimens. Such targets will likely represent ‘common checkpoints’ of inflammation, for example key components or transduction cascades of the signalling pathways involved. Emerging evidence supports involvement of the non‐canonical Wnt signalling pathways in the development of both PsO and PsA, especially the Wnt5a‐activated signalling cascades. These, together with interlinked factors, are crucial in the interactions among keratinocytes, immune cells and inflammatory factors in PsO, as well as among chondrocytes, osteoblasts and osteoclasts that trigger both subchondral bone remodelling and cartilage catabolism in PsA. This review focuses on the pathological role of Wnt5a signalling and its interaction with other interlinked pathways in both PsO and PsA, and also on the main challenges for future research, particularly with respect to molecules targeting Wnt signalling pathways for the treatment of PsO and PsA. 相似文献
69.
为了探讨大麻素受体1基因(Cannabinoid receptor 1,CNR1)3个SNP位点(rs6454674、rs1049353和rs806368)、谷氨酸脱羧酶1基因(Glutamate decarboxylase 1,GAD1)3个SNP位点(rs1978340、rs3791878和rs11542313)、脑源性神经营养因子基因(Brain-derived neurotrophic factor,BDNF)2个SNP位点(rs6265和rs13306221)与云南傣族男性海洛因依赖的相关性,文章采用病例对照关联分析,建立8-SNPs复合扩增体系,应用SNaPshot方法检测165例傣族男性海洛因依赖患者和170例健康傣族男性CNR1、GAD1和BDNF基因8个SNPs位点基因型,采用SPSS17.0、Haploview4.2、PHASE2.1和MDR软件进行统计学分析。结果显示,rs13306221基因型频率在海洛因依赖组和对照组中的差异具有统计学意义(P<0.025),海洛因依赖组rs6265 A等位基因显著高于对照组(P<0.05),由rs1978340-rs3791878-rs11542313构建的T-A-C、C-C-C、C-C-T和T-C-C单体型及rs6265-rs13306221构建的A-G单体型频率在海洛因依赖组及对照组中差异具有统计学意义(P<0.05),海洛因依赖组T-A-C、C-C-T和A-G单体型频率明显高于对照组,GAD1基因rs1978340与rs3791878之间可能存在强协同的交互作用。结果表明,CNR1基因rs1049353多态性、GAD1基因rs1978340和rs11542313多态性以及BDNF基因rs6265和rs13306221多态性与云南傣族男性海洛因依赖相关联,并且携带rs6265 A等位基因的个体可能更容易对海洛因产生依赖。 相似文献
70.
石羊河下游退耕地土壤微生物变化及土壤酶活性 总被引:9,自引:0,他引:9
采用时空替代法,对石羊河下游不同年限(1,2,3,4,5,8,15,24、31 a)退耕地土壤微生物(细菌、真菌和放线菌)数量、生物量(碳、氮和磷)及土壤酶(过氧化氢酶、蔗糖酶、脲酶和磷酸酶)活性变化及三者的相关性进行了测定和分析。结果表明,在退耕1—31 a的9个样地样方中土壤三大类微生物数量以细菌最高,放线菌次之,真菌最低。总体来看,三大土壤微生物数量的加权平均值最大值均在退耕后的前8 a。土壤微生物生物量碳在退耕初期随着退耕年限的增加而减小,退耕4 a后逐渐增大,退耕24 a期间达到了加权平均值的最大,最后趋于稳定;土壤微生物生物量氮在退耕初期随着退耕年限的增加而增加,退耕4 a加权平均值的最大值出现,随后逐渐减小的趋势,并且不同退耕年限土壤微生物生物量氮差异显著;土壤微生物生物量磷在退耕初期随着退耕年限的增加而增加,退耕8 a前后加权平均值达到最大值,随后逐渐减小,最终趋于稳定。土壤酶活性总趋势随着退耕地自然演替时间的增加呈波动式下降。不同土壤层次(0—10 cm,10—20 cm,20—30 cm及30—40 cm),土壤微生物数量、生物量及土壤酶活性随土层深度显著降低,并且表层土壤微生物生物量及土壤酶活性占有较大比例。土壤微生物及土壤酶活性的变化是一个极其缓慢的互动过程,存在着互相回馈的响应,特别是真菌与放线菌、微生物量氮及蔗糖酶,放线菌与过氧化氢酶、蔗糖酶,微生物量碳与磷酸酶,微生物量氮与脲酶,微生物量磷与蔗糖酶均存在极显著的相关性。总体来看在退耕年限4—5 a前,有利于土壤发育,退耕后期土壤肥力呈下降的趋势。 相似文献