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Receptor protein-tyrosine kinases, through phosphorylation of specific tyrosine residues, generate high-affinity binding sites which direct assembly of multienzyme signalling complexes. Many of these signalling proteins, including phospholipase C gamma, GTPase-activating protein and phosphatidylinositol-3-OH kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and specificity to tyrosine-phosphorylated sequences. The critical role played by SH2 domains in signalling has been highlighted by recent studies showing that mutation of specific phosphorylation sites on the platelet-derived growth factor receptor impair its association with phosphatidylinositol-3-OH kinase, preventing growth factor-induced mitogenesis. Here we report the solution structure of an isolated SH2 domain from the 85K regulatory subunit of phosphatidylinositol-3-OH kinase, determined using multidimensional nuclear magnetic resonance spectroscopy. The structure is characterized by a central region of beta-sheet flanked by two alpha-helices, with a highly flexible loop close to functionally important residues previously identified by site-directed mutagenesis.  相似文献   

3.
Actin cables and epidermal movement in embryonic wound healing.   总被引:11,自引:0,他引:11  
P Martin  J Lewis 《Nature》1992,360(6400):179-183
Skin wounds in embryos heal rapidly and perfectly. Even though the epidermis appears to be stretched taut over the surface of a structure such as a growing limb bud, its response to wounding is to close over the lesion, rather than to gape more widely. In adult wounds, the epidermis seems to migrate by means of lamellipodia, crawling over the exposed connective tissue. But in embryonic wounds we do not see lamellipodia. The epidermis at the edge of the wound looks smooth, as though under a circumferential tension. Here we show that a cable of filamentous actin appears to run continuously around most of the wound margin. It is confined to the single row of basal cells at the free edge of the epidermis. We suggest that the actin cable acts as a contractile 'purse string' to close up the embryonic wound.  相似文献   

4.
L Varticovski  B Druker  D Morrison  L Cantley  T Roberts 《Nature》1989,342(6250):699-702
Colony stimulating factor-1 (CSF-1) is a lineage-specific growth factor required for proliferation and survival of mononuclear phagocytes and their precursors. The CSF-1 receptor belongs to a family of ligand-activated protein-tyrosine kinases. Activation of the platelet-derived growth factor receptor, but not the CSF-1 receptor, leads to an increase in phospholipase C activity and a subsequent elevation in intracellular calcium. Recent studies have shown that a novel phosphoinositol (PtdIns) kinase, termed PtdIns-3 kinase, is stimulated by the platelet-derived growth factor receptor and certain oncogenes in the protein-tyrosine kinase family. PtdIns-3 kinase phosphorylates the D-3 hydroxyl position of the inositol ring of PtdIns, and its products do not participate in the generation of the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). Here we report that addition of CSF-1 is followed by activation of PtdIns-3 kinase in a macrophage cell line (P388 D1), which contains CSF-1 receptors, and in BALB/c fibroblasts made to express the human CSF-1 receptor. Furthermore, we show that activation of the CSF-1 receptor results in the accumulation in intact cells of polyphosphoinositides phosphorylated at the D-3 position of the inositol ring. Thus activation of the CSF-1 receptor stimulates PtdIns-3 kinase activity, indicating a novel pathway for CSF-1 receptor-mediated signal transduction.  相似文献   

5.
利用有柄石韦(Pyrrosia petiolosa,P.petiolosa)试制药膏,在动物水平研究其抗菌及促伤口愈合的作用.将有柄石韦制备成药膏,构建大鼠皮肤切除创伤模型并随机分为单纯创伤组和金黄色葡萄球菌(Staphylococcus aureus,S.aureus)感染组.各组分别经自然恢复、P.petiolosa药膏、京万红软膏处理后检测大鼠体重与进食情况、创面愈合情况、创面组织病理情况及血清炎性因子的表达情况.结果显示,不同处理组大鼠体重与进食量无显著变化;创面愈合及组织病理学分析显示P.petiolosa药膏可促进单纯创伤组及S.aureus感染组伤口愈合;ELISA结果显示P.petiolosa药膏在致创前期可明显降低炎性反应.结果表明,这款自主研发的以P.petiolosa为主要原料的中药药膏具有很好的拮抗S.aureus和促进伤口愈合的效果.  相似文献   

6.
本研究通过优化小鼠白介素24(mIL-24)基因序列,构建以Fc-tag为标签的mIL-24-Fc融合蛋白.对CHO进行MTX分级加压筛选,获得了稳定、高表达mIL-24-Fc蛋白的阳性克隆,同时优化了CHO细胞无血清驯化与稳定表达蛋白体系.经protein A亲和层析纯化mIL-24-Fc蛋白并利用AP binding实验检测生物学活性后,小鼠皮内注射mIL-24-Fc蛋白和伤口愈合实验证明:注射mIL-24-Fc蛋白后,小鼠表皮产生2~3层细胞增生,伤口愈合速度加快.  相似文献   

7.
目的:探讨剖宫产不同皮肤切口与伤口愈合有无关系。方法:1995年1月至2002年6月,延安市宝塔区医院做剖宫产术140例,其中70例皮肤为横切口,70例为纵切口,术前准备、术后护理及预防用抗菌素均一致。结果:横切口甲级愈合68例,乙级愈合3例,丙级愈合2例。结论:横切口甲级愈合率97.2%,纵切口甲级愈合率92.9%,横切口甲级愈合率较纵切口愈合率高。  相似文献   

8.
The eight catalytic subunits of the mammalian phosphoinositide-3-OH kinase (PI(3)K) family form the backbone of an evolutionarily conserved signalling pathway; however, the roles of most PI(3)K isoforms in organismal physiology and disease are unknown. To delineate the role of p110alpha, a ubiquitously expressed PI(3)K involved in tyrosine kinase and Ras signalling, here we generated mice carrying a knockin mutation (D933A) that abrogates p110alpha kinase activity. Homozygosity for this kinase-dead p110alpha led to embryonic lethality. Mice heterozygous for this mutation were viable and fertile, but displayed severely blunted signalling via insulin-receptor substrate (IRS) proteins, key mediators of insulin, insulin-like growth factor-1 and leptin action. Defective responsiveness to these hormones led to reduced somatic growth, hyperinsulinaemia, glucose intolerance, hyperphagia and increased adiposity in mice heterozygous for the D933A mutation. This signalling function of p110alpha derives from its highly selective recruitment and activation to IRS signalling complexes compared to p110beta, the other broadly expressed PI(3)K isoform, which did not contribute to IRS-associated PI(3)K activity. p110alpha was the principal IRS-associated PI(3)K in cancer cell lines. These findings demonstrate a critical role for p110alpha in growth factor and metabolic signalling and also suggest an explanation for selective mutation or overexpression of p110alpha in a variety of cancers.  相似文献   

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10.
目的:探讨Caspase-3和FIEN蛋白在口腔扁平苔藓病变发生发展中的作用及两者间的关系。方法:采用S—P免疫组化方法对28例口腔扁平苔藓及5例正常口腔黏膜中Caspase-3和PTEN蛋白表达进行检测。结果:口腔扁平苔藓病损中Caspase-3的阳性率上皮层和固有层均为100%,与正常口腔黏膜相比,表达有显著统计学意义(P〈0.01)。口腔扁平苔藓病损中PTEN蛋白阳性率为100%,与正常口腔黏膜相比,无统计学差异(P〉0.05)。口腔扁平苔藓中Caspase-3与PTEN蛋白表达呈正相关,(P〈0.05)。结论:Caspase-3和PTEN蛋白均参与口腔扁平苔藓病变的发生及发展过程,且两者之间具有相关性。  相似文献   

11.
以乙二醇为溶剂、Na2S为成核剂、聚乙烯吡喏烷酮(PVP)和Na2CO3为修饰剂,采用醇热法制备不同形貌的Ag纳米晶。通过调节反应时间、Na2CO3浓度、滴加速率以及起始滴加时间等来调控Ag纳米晶的微结构。利用场发射扫描电子显微镜(FESEM)和紫外-可见光(UV-vis)吸收光谱对Ag纳米晶的形貌和尺寸以及局域表面等离子特性(LSPR)进行表征。结果表明:浓度为50μmol/L的Na2CO3,在AgNO3滴加完毕后5.5 min时以2 mL/min的速率滴加到体系中反应3 h,能够得到平均颗粒尺寸为60 nm、尺寸分布均匀的截角立方Ag纳米晶。  相似文献   

12.
基于熵测度和SQP方法的跳频信号时频表示   总被引:1,自引:0,他引:1  
提出了一种基于三阶Renyi熵测度的双向高斯核函数,分析了核参数与熵测度的变化规律,并利用逐步二次规划法对其进行优化.与信号相关径向高斯核函数时频分布相比,该方法不需要任何先验假定,能够有效反映交叉项在时频分布中的大小,获取优化的时频表示,从而提高了跳频信号的参数估计精度,同时可以适应低信噪比环境.仿真结果验证了基于熵测度优化时频表示法分析跳频信号的有效性和实用性.  相似文献   

13.
阐述了高职院校培养学生维修创新能力的重要性和必要性,指出排除故障训练应从兴趣着手,采用科学的故障树分析法,由浅入深,逐步展开.  相似文献   

14.
为了选择与无刷直流电动机匹配的调速控制方式,采用了基于可编程片上系统技术的有限状态机分析法.对构建调速控制信号的几个关键环节,如转子空间位置信号调理,脉宽恒定而周期跟踪转速的PWM波形发生器以及控制定子电流正、反向与换相的主控信号等,进行了波形描述和时序分析,并完成了相应数字硬件的设计.为系统的综合设计与实施提供了方案流程,硬件配置和参数设定方面的参照基础.  相似文献   

15.
Silver sulfadiazine(SSD) particles in homogeneous dispersion state were prepared by an ultrasonic method and then nano- and microparticles were separated using centrifugation. SSD particles with narrow size distribution were impregnated with bacterial cellulose(BC) to produce BC–SSD composite membrane used as burn wound dressing. A scanning electron microscope(SEM) was used to examine the surface morphology of BC–SSD membranes. The incorporation of SSD in BC–SSD was confirmed by X-ray diffraction(XRD). Antimicrobial tests in vitro indicated that BC–SSD showed excellent antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. The effects of BC–SSD on burn wound healing were assessed by rat models. The comparative study confirmed that the wound treated with BC–SSD showed high healing rate. The bacteria count in BC–SSD group was far less than control group. Histological analysis showed that epithelialization progressed better in wound treated with BC–SSD. These values demonstrated that the BC–SSD composite membrane could be a promising wound dressing for burn.  相似文献   

16.
井地电法的三维正反演研究   总被引:6,自引:0,他引:6  
通过简化井地电法模型为垂直有限长线电流源作用下的三维地下介质模型,利用三维有限元法实现了垂直有限长线电流源作用下的三维地下介质电场的正演计算。应用非线性阻尼最小二乘迭代算法实现了地表电位数据的地下目标层电阻率反演,通过简化模型对相应计算程序进行了检验,证实了程序的可靠性。用给定模型正演得到的地表“理论合成数据”来反演地下异常体,并对数据测量范围和干扰水平对反演的影响进行了讨论。该研究可为提高井地电法反演质量提供部分理论指导依据。  相似文献   

17.
通过简化井地电法模型为垂直有限长线电流源作用下的三维地下介质模型,利用三维有限元法实现了垂直有限长线电流源作用下的三维地下介质电场的正演计算。应用非线性阻尼最小二乘迭代算法实现了地表电位数据的地下目标层电阻率反演,通过简化模型对相应计算程序进行了检验,证实了程序的可靠性。用给定模型正演得到的地表"理论合成数据"来反演地下异常体,并对数据测量范围和干扰水平对反演的影响进行了讨论。该研究可为提高井地电法反演质量提供部分理论指导依据。  相似文献   

18.
We use extended Huckel methods of molecular orbitds and crystal orbitals (EHMO/CO) to calculate the two-dimensional band structures of highly oriented trans-polyacetylene (PA) undoped and doped with SO3. According to the energy band theory of solids, we explain the changes of band gap (Eg) and bandwidth (BW) from undoped PA to SO3-doped PA, and discuss the electrical anisotropy of oriented trans-polyacetylene doped with SO3. The calculated results show that the conductivity anisotropy ratio (σ///σ⊥) is determined by Eg and BW in the directions both parallel (σ//) and perpendicular (σ⊥) to the PA chains, respectively. The conductivity anisotropy ratio σ///σ⊥ decreases when PA is doped with SO3, because the dopant plays a conjugated bridge role between the interchains of PA, and makes the dopant itself and PA chains show a strong interchain coupling. The theoretical results for undoped and doped PA are in good agreement with experimental ones.  相似文献   

19.
针对网络诱导时延的不确定特性,提出了一种递阶多模型切换控制的策略,以减小网络诱导时延不确定性带来的不利影响.考虑到网络带宽有限,为了减少全局控制信息的传送,将控制系统分为主控制器级和局部控制器级两层递阶结构.在系统运行过程中,根据网络诱导时延和当前子系统最大允许时延的关系选择最佳的局部控制器.应用公共李雅普诺夫函数法,分析得到了系统稳定的条件.通过数值仿真比较验证了该算法的有效性.  相似文献   

20.
We use extended Hückel methods of molecular orbitds and crystal orbitals (EHMO/CO) to calculate the two-dimensional band structures of highly oriented trans-polyacetylene (PA) undoped and doped with SO3. According to the energy band theory of solids, we explain the changes of band gap (Eg) and bandwidth (BW) from undoped PA to SO3-doped PA, and discuss the electrical anisotropy of oriented trans-polyacetylene doped with SO3. The calculated results show that the conductivity anisotropy ratio (σ∥/σ┴) is determined by Eg and BW in the directions both parallel (σ∥) and perpendicular (σ┴) to the PA chains, respectively. The conductivity anisotropy ratio σ∥/σ┴ decreases when PA is doped with SO3, because the dopant plays a conjugated bridge role between the interchains of PA, and makes the dopant itself and PA chains show a strong interchain coupling. The theoretical results for undoped and doped PA are in good agreement with experimental ones.  相似文献   

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