Wnt-beta-catenin signaling initiates taste papilla development

Fungiform taste papillae form a regular array on the dorsal tongue. Taste buds arise from papilla epithelium and, unusually for epithelial derivatives, synapse with neurons, release neurotransmitters and generate receptor and action potentials. Despite the importance of taste as one of our five senses, genetic analyses of taste papilla and bud development are lacking. We demonstrate that Wnt-beta-catenin signaling is activated in developing fungiform placodes and taste bud cells. A dominant stabilizing mutation of epithelial beta-catenin causes massive overproduction of enlarged fungiform papillae and taste buds. Likewise, genetic deletion of epithelial beta-catenin or inhibition of Wnt-beta-catenin signaling by ectopic dickkopf1 (Dkk1) blocks initiation of fungiform papilla morphogenesis. Ectopic papillae are innervated in the stabilizing beta-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation. Thus, Wnt-beta-catenin signaling is critical for fungiform papilla and taste bud development. Altered regulation of this pathway may underlie evolutionary changes in taste papilla patterning.     

On the self-association potential of transmembrane tight junction proteins

Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5 also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of occludin, dimerization of its cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second extracellular loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction assembly is supported. Received 6 October 2005; received after revision 14 December 2005; accepted 27 December 2005 †These authors contributed equally to this work.     

Regulation of cell adhesion by PP2A and SV40 small tumor antigen: An important link to cell transformation

The serine/threonine protein phosphatase 2A (PP2A) represents a large family of highly conserved heterotrimeric enzymes. Their critical importance in cell homeostasis is underlined by the fact that they are targets of natural toxins like the tumor promoter okadaic acid, and of simian virus 40 small tumor antigen (SV40 small t), a viral protein known to promote cell transformation. Furthermore, mutated or lower expression levels of PP2A subunits have been found in certain cancers. One major known event in PP2A-dependent cell transformation is the alteration of key signaling pathways that control cell growth and survival. In this review, we focus on how PP2A enzymes also affect cell adhesion and cytoskeletal dynamics, the disruption of which is linked to loss of cell polarity, increased cell motility and invasiveness. We also examine how those various pathways participate in the transforming activity of SV40 small t. Received 29 June 2006; received after revision 3 August 2006; accepted 20 September 2006     

Cancer and blood coagulation

In human patients, blood coagulation disorders often associate with cancer, even in its early stages. Recently, in vitro and in vivo experimental models have shown that oncogene expression, or inactivation of tumour suppressor genes, upregulate genes that control blood coagulation. These studies suggest that activation of blood clotting, leading to peritumoral fibrin deposition, is instrumental in cancer development. Fibrin can indeed build up a provisional matrix, supporting the invasive growth of neoplastic tissues and blood vessels. Interference with blood coagulation can thus be considered as part of a multifaceted therapeutic approach to cancer. Received 30 November 2005; received after revision 7 February 2005; accepted 8 February 2006     

Functional interactions of protein kinase A and C in signalling networks: a recapitulation

On the basis of evidence collected from the literature, we propose a general model by which protein kinase (PK) A and the different PKC isoforms can inversely affect cell growth. Molecular switches, which are able to direct the signal towards antiproliferative or mitogenic pathways, are the different isoforms of Raf and PKC. Conflicting data are also reported and discussed in an attempt to reconcile them. Received 10 November 2005; received after revision 28 December 2005; accepted 3 January 2006     

世界优秀男子110 m栏运动员成绩变化分析

采用文献资料调查、数理统计等科研方法, 对1997年世界田径锦标赛男子110 m栏前 7 名运动员的成绩进行相关分析, 揭示当今男子110 m栏全程速度变化的规律和特点, 并对近 4 年来世界优秀男子 110 m栏运动员与我国男子110 m栏运动员的成绩进行对比分析, 希望能对我国男子110 m栏的训练提供一些新的参考和启示.     

喷动流化床射流穿透度智能拟合

在三维冷态试验台架上对喷动流化床射流穿透度进行了实验研究,得出了射流穿透度随喷口尺寸、载气密度、喷动气速的增大而增大,随静止床高、颗粒尺寸、颗粒密度、流化气率、载气黏度的增大而减小的结论.在实验研究的基础上利用最小二乘支持向量机对射流穿透度与喷动流化床主要设计参数之间的数值关系进行了智能拟合,并利用自适应遗传算法优化了最小二乘支持向量机的初始参数.通过15个预测样本的检验,最小二乘支持向量机模型的预测平均相对误差减小至4.0%,其性能大大优于常用的经验公式以及神经网络.     

探讨带参数微分方程边值问题的解法

主要讨论带参数微分方程边值问题的逼近值及渐近值解法,并且利用基础解系、边值函数等概念,解决了带参数的微分方程中参数充分小的范围内解的变化趋势.