Medulloblastoma growth inhibition by hedgehog pathway blockade

Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.     

EGFR和K-Ras在上皮性卵巢癌组织中的表达及临床意义

\t\t\t\t\t目的\t\t\t\t\t探讨促卵泡激素受体结合抑制剂(FRBI)对绵羊卵母细胞中K-Ras、c-Myc及FSHR mRNA和蛋白质水平的影响,进一步阐明FRBI是否通过IP3信号通路发挥作用。\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t方法\t\t\t\t\t将卵母细胞置于10 IU/mL的FSH和不同质量浓度FRBI (0、10、20、30和40 μg/mL)的体外成熟培养基中培养24 h。应用ELISA检测IVM培养液中K-Ras、c-Myc、cAMP、FSH和IP3的含量。qRT-PCR和Western-blot检测卵母细胞中FSHR mRNA和蛋白质的水平。\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t结果\t\t\t\t\t至24 h时,随着FRBI剂量增加,COM-1组至COM-3组c-Myc质量浓度逐渐降低,COM-3显著低于FSH组(P<0.05),COM-4组24 h的K-Ras质量浓度显著低于阴性对照组(CG)和FSH组(P<0.05);COM组中,FSHR mRNA和蛋白表达水平随着FRBI剂量的增加而下降,高剂量组(COM-4) mRNA与蛋白质表达水平显著低于FSH组(P<0.05)。cAMP和IP3含量随FRBI剂量增加而递减,COM-4组IP3显著低于CG组(P<0.05)。\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t结论\t\t\t\t\t在FSH存在下,FRBI可减少K-Ras和c-Myc的产生,抑制卵母细胞的FSHR水平,FRBI可能通过IP3通路发挥作用。\t\t\t\t     

Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr308 in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser473 within the carboxyl-terminal hydrophobic motif by an unknown kinase. We show that in Drosophila and human cells the target of rapamycin (TOR) kinase and its associated protein rictor are necessary for Ser473 phosphorylation and that a reduction in rictor or mammalian TOR (mTOR) expression inhibited an Akt/PKB effector. The rictor-mTOR complex directly phosphorylated Akt/PKB on Ser473 in vitro and facilitated Thr308 phosphorylation by PDK1. Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation.     

应用PCR方法鉴别绵羊产单核细胞李氏杆菌

结合溶血试验和动物试验,应用PCR鉴别新疆5个地区从绵羊实质器官及饲草中分离到的7株李氏杆菌,它们分别是90SB 1、90SB 2、90SB 5、90SS1、125SL 1、G 1和饲草李。试验结果表明,前5株为产单核细胞李氏杆菌。     

通过双重PCR方法区分坏死梭杆菌亚种

基于已发表的坏死梭杆菌白细胞毒素启动子区序列,设计3条特异性引物L7、L8和L9。L7和L8分别与Fnn和Fnf的特异性序列结合,L9与两个亚种序列相匹配。分别扩增出1 076bp和809bp的特异性片段。试验结果表明,这些引物具有高度的特异性和敏感性,能够检测坏死梭杆菌基因组DNA的最小量为10pg/μL,建立的双重PCR体系可用于区分坏死梭杆菌亚种。     

Phytohemagglutinin: inhibition of the agglutinating activity by N-acetyl-D-galactosamine

The effect of simple sugars on the agglutinating activity of phytohemagglutinin was studied. N-Acetyl-d-galactosamine selectively inhibits the agglutination of leukocytes and erythro- cytes by phytohemagglutinin.     

Angiotensin pressor inhibition by aldosterone in the rabbit

Rabbits pretreated with aldosterone exhibited lessened response to the pressor agent angiotensin. This observation may help to explain the absence of hypertension in certain instances in which both the formation of angiotensin and the secretion of aldosterone are above normal.     

Leptin通过JAK-STAT3通路抑制原代大鼠脂肪细胞perilipin mRNA的表达

【目的】探讨瘦素(Leptin)影响大鼠脂肪细胞perilipin、ADRP和TIP47 mRNA表达的分子机理。【方法】以体外培养的原代大鼠脂肪细胞为研究对象,用50 ng/mL Leptin及Leptin与JAK-STAT3通路抑制剂(AG490)、MEK通路抑制剂(U0126)、PPARgamma激活剂(罗格列酮(Ros))联合处理原代大鼠脂肪细胞3 h,提取总RNA,半定量(Semi-quantitative,SQ)RT-PCR法检测PPAR gamma、perilipin、ADRP和TIP47 mRNA的表达情况。【结果】阻断JAK-STAT3通路,可以减弱50 ng/mL Leptin对原代大鼠脂肪细胞perilipin mRNA表达的抑制作用(P<0.05),但加剧了Leptin对大鼠脂肪细胞ADRP和TIP47 mRNA表达的抑制(P<0.05);阻断MEK通路可以加剧Leptin对大鼠脂肪细胞perilipin、ADRP和PPAR gamma mRNA表达的抑制作用(P<0.05)。【结论】Leptin通过JAK-STAT3通路抑制原代大鼠脂肪细胞perilipin mRNA的表达。     

Enhancement of flicker by lateral inhibition

Sinusoidal modulation of illumination on the compound eye of the horseshoe crab, Limulus, produces a corresponding variation in the rate of discharge of optic nerve impulses. Increasing the area of illumination decreases the variation at low frequencies of modulation, but unexpectedly enhances-or "amplifies"-the variation at the intermediate frequencies to which the eye is most sensitive. Both effects must result from inhibition since it is the only significant lateral influence in this eye.     

Bradykinin inhibition by butylated hydroxyanisole

Concentrations of butylated hydroxyanisole as low as 8 x 10(-9) mole per liter can inhibit detectably the contraction of smooth muscle elicited by bradykinin. The mechanism of the inhibitory effect of this food grade anti-oxidant is apparently complex, and the effect is only partially reversible.     

应用RAPD技术区分3种麻蝇

[目的]探求应用RAPD技术区分麻蝇种类。[方法]用RAPD技术对黑尾黑麻蝇、棕尾别麻蝇、红尾粪麻蝇进行扩增,并对反应体系和程序进行一系列优化,从中选出可以区分3种麻蝇的引物和特异性条带。[结果]引物S247、S266对3种麻蝇扩增结果存在显著差异。[结论]RAPD技术是一种可以有效区分3种麻蝇的方法。     

RAPD技术在鸡球虫虫株鉴定上的应用

采用 RAPD 技术对 E.tenella 早熟株、鸡胚株、亲本毒抹和田间分离的抗药株进行研究,发现本研究选育的 E.tenella 早熟株与亲本毒株间 DNA 多态性存在着差异,证实该早熟侏已发生了遗传变异,但变异程度不大;而鸡胚株及抗药株却比早熟株的变异程度大。建议 RAPD 技术可用于艾美耳球虫株间差异及其球虫株间关系距离的检测.对经细胞培养的 E.acervulina 早熟株及其毒株和抗药株的基因组 DNA 进行多态性比较研究,发现该3株球虫间的变异程度大于 E.tenella 各虫株间的变异,即不同来源的 E.ac-ervulina 各虫株间的相似性小于 E.tenella 各虫株间的相似性,表明不同球虫其种内变异程度不一致。本研究结果表明 RAPD 技术可作为球虫株间变异的分子标记方法及其球虫株间关系距离的检测手段。     

Phosphorylation and regulation of Raf by Akt (protein kinase B)

Activation of the protein kinase Raf can lead to opposing cellular responses such as proliferation, growth arrest, apoptosis, or differentiation. Akt (protein kinase B), a member of a different signaling pathway that also regulates these responses, interacted with Raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of Raf by Akt inhibited activation of the Raf-MEK-ERK signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation. These observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt.     

Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting

beta-Secretase plays a critical role in beta-amyloid formation and thus provides a therapeutic target for Alzheimer's disease. Inhibitor design has usually focused on active-site binding, neglecting the subcellular localization of active enzyme. We have addressed this issue by synthesizing a membrane-anchored version of a beta-secretase transition-state inhibitor by linking it to a sterol moiety. Thus, we targeted the inhibitor to active beta-secretase found in endosomes and also reduced the dimensionality of the inhibitor, increasing its local membrane concentration. This inhibitor reduced enzyme activity much more efficiently than did the free inhibitor in cultured cells and in vivo. In addition to effectively targeting beta-secretase, this strategy could also be used in designing potent drugs against other membrane protein targets.     

取对数求导法释疑

对一元函数取对数求导法的两种常见类型之一——由若干因式的积、商、幂组成的函数的取对数求导作了进一步的讨论,对含有负因式、零因式时取对数求导也得出相应的结论。