The expansion of GPCR transactivation-dependent signalling to include serine/threonine kinase receptors represents a new cell signalling frontier

G protein-coupled receptor (GPCR) signalling is mediated through transactivation-independent signalling pathways or the transactivation of protein tyrosine kinase receptors and the recently reported activation of the serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Since the original observation of GPCR transactivation of protein tyrosine kinase receptors, there has been considerable work on the mechanism of transactivation and several pathways are prominent. These pathways include the “triple membrane bypass” pathway and the generation of reactive oxygen species. The recent recognition of GPCR transactivation of serine/threonine kinase receptors enormously broadens the GPCR signalling paradigm. It may be predicted that the transactivation of serine/threonine kinase receptors would have mechanistic similarities with transactivation of tyrosine kinase pathways; however, initial studies suggest that these two transactivation pathways are mechanistically distinct. Important questions are the relative importance of tyrosine and serine/threonine transactivation pathways, the contribution of transactivation to overall GPCR signalling, mechanisms of transactivation and the range of cell types in which this phenomenon occurs. The ultimate significance of transactivation-dependent signalling remains to be defined but it appears to be prominent and if so will represent a new cell signalling frontier.     

Compartmental analysis of efflux of extracellular space markers in rabbit detrusor muscle

Zusammenfassung Mit Hilfe des Computers wurde die Abgabe von [¹⁴C]-markiertem Mannit, Succrose und Inulin aus isoliertem Kaninchen-Detrusormuskel analysiert. Alle drei Verbindungen werden aus mindestens drei Abschnitten abgegeben und aus einer gebundenen Fraktion gelöst. Die Grösse des am raschesten von Mannit und Succrose beanspruchten Abschnittes entsprich derjenigen des Inulins.

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Supported by a grant from the Medical Research Council of Canada.     

Forecasting the Dubai financial market with a combination of momentum effect with a deep belief network

Applying recent advances in machine learning techniques, we propose a hybrid model to forecast the Dubai financial market general index. Particularly, we exploit a deep belief networks model that applies a restricted Boltzmann machine as its main component in combination with momentum effects. We also introduce an innovative way of selecting the inputs by using momentum effects. With this hybrid methodology we generate a prediction model along with a comparison of three different linear models. The results obtained from the hybrid model are better and more stable than the three linear models. The findings support that the hybrid model we applied will find their way into finance because of their reliability and good performance.     

Self-incompatibility in Papaver targets soluble inorganic pyrophosphatases in pollen

In higher plants, sexual reproduction involves interactions between pollen and pistil. A key mechanism to prevent inbreeding is self-incompatibility through rejection of incompatible ('self') pollen. In Papaver rhoeas, S proteins encoded by the stigma interact with incompatible pollen, triggering a Ca2+-dependent signalling network resulting in pollen tube inhibition and programmed cell death. The cytosolic phosphoprotein p26.1, which has been identified in incompatible pollen, shows rapid, self-incompatibility-induced Ca2+-dependent hyperphosphorylation in vivo. Here we show that p26.1 comprises two proteins, Pr-p26.1a and Pr-p26.1b, which are soluble inorganic pyrophosphatases (sPPases). These proteins have classic Mg2+-dependent sPPase activity, which is inhibited by Ca2+, and unexpectedly can be phosphorylated in vitro. We show that phosphorylation inhibits sPPase activity, establishing a previously unknown mechanism for regulating eukaryotic sPPases. Reduced sPPase activity is predicted to result in the inhibition of many biosynthetic pathways, suggesting that there may be additional mechanisms of self-incompatibility-mediated pollen tube inhibition. We provide evidence that sPPases are required for growth and that self-incompatibility results in an increase in inorganic pyrophosphate, implying a functional role for Pr-p26.1.     

Ga<Subscript>q</Subscript> proteins: molecular pharmacology and therapeutic potential

Seven transmembrane G protein-coupled receptors (GPCRs) have gained much interest in recent years as it is the largest class among cell surface receptors. G proteins lie in the heart of GPCRs signalling and therefore can be therapeutically targeted to overcome complexities in GPCR responses and signalling. G proteins are classified into four families (G_i, G_s, G_12/13 and G_q); G_q is further subdivided into four classes. Among them G_αq and G_αq/11 isoforms are most crucial and ubiquitously expressed; these isoforms are almost 88% similar at their amino acid sequence but may exhibit functional divergences. However, uncertainties often arise about G_αq and G_αq/11 inhibitors, these G proteins might also have suitability to the invention of novel-specific inhibitors for each isoforms. YM-254890 and UBO-QIC are discovered as potent inhibitors of G_αq functions and also investigated in thrombin protease-activated receptor (PAR)-1 inhibitors and platelet aggregation inhibition. The most likely G protein involved in PAR-1 stimulates responses is one of the G_αq family isoforms. In this review, we highlight the molecular structures and pharmacological responses of G_αq family which may reflect the biochemical and molecular role of G_αq and G_αq/11. The advanced understanding of G_αq and G_αq/11 role in GPCR signalling may shed light on our understanding on cell biology, cellular physiology and pathophysiology and also lead to the development of novel therapeutic agents for a number of diseases.     

字符级的维吾尔语形态协同分析方法

针对维吾尔语中构形词缀种类多、构形复杂以及发生音变现象等问题, 提出一种基于字符级的维吾尔语形态协同分析方法。该方法最大的特点是同时进行维吾尔语的形态切分、形态标注以及音变还原, 将词素边界、形态标记以及音变信息用一个复合标记描述, 采用字符序列的标注方法进行训练。实验结果显示, 形态切分、形态标注及音变还原的正确率分别达到96.39%, 92.78%和99.79%, 系统总体正确率达92.59%。