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.     

θ环填料塔中单乙醇胺吸收CO2传质性能研究

在乱堆θ环不锈钢填料的自制填料塔中,使用单乙醇胺(MEA)作为吸收剂,研究MEA脱除CO2的去除率和总体积传质系数KGav,考察了贫液中CO2负载量、吸收剂浓度、液体流量、吸收温度等不同参数对总体积传质系数的影响.实验结果表明,KGav随贫液中CO2负载量的增大而减小,随吸收剂浓度、液体流量的增大而增大;且进料温度在3...     

BOOK REVIEWS

Rethinking the Fifth Discipline: Learning Within the Unknowable by Robert Louis Flood. Sami Potatoes: Living with Reindeer and Perestroika by Michael Robinson and Karim-Aly Kassam. The Self Managing Organization: How Leading Companies Are Transforming the Work of Teams for Real Impact by Ronald E. Purser and Steven Cabana.     

广西产眼镜王蛇毒α-神经毒素基因的分子克隆及序列分析

为获得眼镜王蛇（Ophiophagus hannah，简称Oh）蛇毒α－神经毒素（α-NT）的基因序列，依据眼镜蛇科不同毒蛇种类来源的α－NT基因有较高的同源性，设计1对上下游引物，为克服引物带来模糊扩增，在蛋白编码部分再设计1对上下游特异引物，用Nacleospin RNA Kit法从3条活眼镜王蛇毒腺中提取mRNA，以3′端引物合成的cDNA作为模板进行PCR扩增反应，测定产物的核苷酸序列，得到全长474bp的眼镜王蛇cDNA基因核苷酸序列。该核苷酸序列的信号肽与眼镜蛇树属Pseudonnaja textilis(Pt)、海蛇Laticauda semifasciata(Ls)100%同源，与眼镜蛇南洋亚种Naja sputatrix (Ns)、银环蛇（Bungarus multicinctus)(Bm)96.8%同源；蛋白密码部分有83．3％与Ns、79．2％与Pt、76．4％与Ls、74．1％与Bm同源。信号肽后紧接着的72个氨基酸有90．3％与已发现的眼镜王蛇毒长链α-NT Toxin a同源，大约有73．6％与Toxin b、69．7％与Oh-4、66．7％与Oh-5、56．9％与Oh-6A和6B同源，并与α－银环蛇毒素54．2％同源。说明新发现的眼镜王蛇cDNA是一条长链α-NT基因。     

Statistical tests on two characteristics of the shapes of cluster diagrams

A cluster diagram is a rooted planar tree that depicts the hierarchical agglomeration of objects into groups of increasing size. On the null hypothesis that at each stage of the clustering procedure all possible joins are equally probable, we derive the probability distributions for two properties of these diagrams: (1)S, the number of single objects previously ungrouped that are joined in the final stages of clustering, and (2)m _k, the number of groups ofk+1 objects that are formed during the process. Ecological applications of statistical tests for these properties are described and illustrated with data from weed communities of Saskatchewan fields.This work was supported by the Natural Sciences and Engineering Research Council of Canada.     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005     

Elucidation of the relationship between enzyme activity and internal motion using a lysozyme stabilized by cavity-filling mutations

We investigated the activity and the internal motions of a stabilized mutant hen lysozyme (HEL) in which the residues M12 and L56 were mutated to L and F, respectively (LF mutant HEL). The result of the activity measurements against glycol chitin at various temperatures suggested that the temperature dependence of the activity of LF mutant HEL shifted to the high-temperature side compared with that of wild-type HEL. The detailed internal motions of LF mutant HEL in the absence and presence of a substrate analogue, (NAG)₃, were examined by model-free analysis at 35°C. The results showed that the internal motions of LF mutant HEL in the presence of (NAG)₃ were drastically restricted compared with those in wild-type HEL. Our findings thus suggested that the mutation to the stabilized lysozyme restricted internal motions required for the enzymatic reaction.Received 8 February 2005; accepted 10 March 2005Y. Yoshida and T. Ohkuri contributed equally to this work.