Molecular mechanisms in therapy of acid-related diseases

Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists. Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007     

Endocrine-dependent expression of circadian clock genes in insects

Current models state that insect peripheral oscillators are directly responsive to light, while mammalian peripheral clock genes are coordinated by a master clock in the brain via intermediate factors, possibly hormonal. We show that the expression levels of two circadian clock genes, period (per) and Par Domain Protein 1 (Pdp1) in the peripheral tissue of an insect model species, the linden bug Pyrrhocoris apterus, are inversely affected by contrasting photoperiods. The effect of photoperiod on per and Pdp1 mRNA levels was found to be mediated by the corpus allatum, an endocrine gland producing juvenile hormone. Our results provide the first experimental evidence for the effect of an endocrine gland on circadian clock gene expression in insects. Received 31 October 2007; received after revision 7 January 2008; accepted 9 January 2008 D. Dolezel, L. Zdechovanova: These authors contributed equally to this work.     

Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives

Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis. Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut may open new therapeutic strategies in hepato-gastrointestinal diseases. Received 15 August 2007; received after revision 1 November 2007; accepted 5 November 2007     

Coilin levels and modifications influence artificial reporter splicing

Cajal bodies (CBs) and Gems are nuclear domains that contain factors responsible for spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis. The marker protein for CBs is coilin. In addition to snRNPs, coilin and other factors, canonical CBs contain the survivor of motor neuron protein (SMN). SMN can also localize to Gems. Considering the important role that coilin plays in the formation and composition of CBs, we tested the splicing efficiency of several cell lines that vary in regards to coilin level and modification using an artificial reporter substrate. We found that cells with both hypomethylated coilin and Gems are more efficient at reporter splicing compared to cells in which SMN localizes to CBs. In contrast, coilin reduction, which induces Gem formation, decreases cell proliferation and artificial reporter splicing. These findings demonstrate that coilin modifications or levels impact artificial reporter splicing, possibly by influencing snRNP biogenesis. Received 26 December 2007; received after revision 5 February 2008; accepted 7 February 2008     

雪灵芝水溶性多糖提取工艺优化及其数学模型的建立

目的 优化雪灵芝水溶性多糖的提取工艺,并建立数学模型.方法 采用水提醇沉法提取雪灵芝水溶性多糖;运用苯酚-硫酸法测定多糖含量;通过单因素实验研究浸提时间、加水比、浸提温度及乙醇浓度对多糖提取率的影响;采用响应面分析法优化提取条件,运用sas软件分析实验数据,建立回归模型.结果 得到雪灵芝水溶性多糖提取的优化工艺参数的最佳取值范围为:浸提温度(94.5～97.5℃);浸提时间(2～2.5h);加水比(43～51v/w).结论 为雪灵芝水溶性多糖提取工艺的优化提供了一定的技术依据,也为其后续研究奠定了基础.     

圆筒直线感应电机研究综述

圆筒型直线感应电动机与普通电动机的区别在于圆筒型直线电动机存在纵向端部效应.在这篇文章中,简要介绍圆筒直线感应电机的发展与结构后,分析了国内外直线电机特别是圆筒直线电机的研究现状,根据分析得出圆筒直线感应电机需要进一步研究的方向.     

Myosin V from head to tail

Myosin V (myoV), a processive cargo transporter, has arguably been the most well-studied unconventional myosin of the past decade. Considerable structural information is available for the motor domain, the IQ motifs with bound calmodulin or light chains, and the cargo-binding globular tail, all of which have been crystallized. The repertoire of adapter proteins that link myoV to a particular cargo is becoming better understood, enabling cellular transport processes to be dissected. MyoV is processive, meaning that it takes many steps on actin filaments without dissociating. Its extended lever arm results in long 36-nm steps, making it ideal for single molecule studies of processive movement. In addition, electron microscopy revealed the structure of the inactive, folded conformation of myoV when it is not transporting cargo. This review provides a background on myoV, and highlights recent discoveries that show why myoV will continue to be an active focus of investigation. Received 31 October 2007; received after revision 4 December 2007; accepted 2 January 2008     

Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology, and Therapeutics

Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

The Xenopus tadpole is a favourable organism for regeneration research because it is suitable for a wide range of micromanipulative procedures and for a wide range of transgenic methods. Combination of these techniques enables genes to be activated or inhibited at specific times and in specific tissue types to a much higher degree than in any other organism capable of regeneration. Regenerating systems include the tail, the limb buds and the lens. The study of tail regeneration has shown that each tissue type supplies the cells for its own replacement: there is no detectable de-differentiation or metaplasia. Signalling systems needed for regeneration include the BMP and Notch signalling pathways, and perhaps also the Wnt and FGF pathways. The limb buds will regenerate completely at early stages, but not once they are fully differentiated. This provides a good opportunity to study the loss of regenerative ability using transgenic methods.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues.