Galectin-3 stabilizes heterogeneous nuclear ribonucleoprotein Q to maintain proliferation of human colon cancer cells

Comparative analysis of proteomes using 5-fluorouracil (5-FU)-resistant human colon cancer cell line revealed that decreased galectin-3 expression was significantly associated with retarded proliferation. However, in the presence of 5-FU proliferation rate of cells with suppressed galectin-3 expression did not differ from that of cells with normal galectin-3 expression, even galectin-3 suppression augmented apoptosis. Mechanism by which galectin-3 regulates cancer cell proliferation has been identified in immunoprecipitates of the anti-galectin-3 antibody. Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) was identified as a protein interacting with galectin-3. Interestingly, while galectin-3 protein was not affected by the hnRNP Q level, its suppression was accompanied by a decrease in hnRNP Q expression. The present study demonstrates that galectin-3 stabilizes hnRNP Q via complex formation, and reduction in the hnRNP Q level leads to slow proliferation and less susceptibility to 5-FU. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. B.C.Yoo; S-H.Hong; These two authors contributed equally to this work. Received 10 September 2008; received after revision 19 October 2008; accepted 07 November 2008     

线性搜索方法的改进

线性搜索是最优化计算中最普遍应用的方法，文中对Ｆｌｅｔｃｈｅｒ线性搜索方法作了改进，它具有减少梯度值计算次数的特点，并用数值结果表明了方法的有效性。     

An increased estimate of the merger rate of double neutron stars from observations of a highly relativistic system

The merger of close binary systems containing two neutron stars should produce a burst of gravitational waves, as predicted by the theory of general relativity. A reliable estimate of the double-neutron-star merger rate in the Galaxy is crucial in order to predict whether current gravity wave detectors will be successful in detecting such bursts. Present estimates of this rate are rather low, because we know of only a few double-neutron-star binaries with merger times less than the age of the Universe. Here we report the discovery of a 22-ms pulsar, PSR J0737-3039, which is a member of a highly relativistic double-neutron-star binary with an orbital period of 2.4 hours. This system will merge in about 85 Myr, a time much shorter than for any other known neutron-star binary. Together with the relatively low radio luminosity of PSR J0737-3039, this timescale implies an order-of-magnitude increase in the predicted merger rate for double-neutron-star systems in our Galaxy (and in the rest of the Universe).     

Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice

Although the question of to whom a male directs his mating attempts is a critical one in social interactions, little is known about the molecular and cellular mechanisms controlling mammalian sexual preference. Here we report that the neurotransmitter 5-hydroxytryptamine (5-HT) is required for male sexual preference. Wild-type male mice preferred females over males, but males lacking central serotonergic neurons lost sexual preference although they were not generally defective in olfaction or in pheromone sensing. A role for 5-HT was demonstrated by the phenotype of mice lacking tryptophan hydroxylase 2 (Tph2), which is required for the first step of 5-HT synthesis in the brain. Thirty-five minutes after the injection of the intermediate 5-hydroxytryptophan (5-HTP), which circumvented Tph2 to restore 5-HT to the wild-type level, adult Tph2 knockout mice also preferred females over males. These results indicate that 5-HT and serotonergic neurons in the adult brain regulate mammalian sexual preference.     

Structural insight into brassinosteroid perception by BRI1

Brassinosteroids are essential phytohormones that have crucial roles in plant growth and development. Perception of brassinosteroids requires an active complex of BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED KINASE 1 (BAK1). Recognized by the extracellular leucine-rich repeat (LRR) domain of BRI1, brassinosteroids induce a phosphorylation-mediated cascade to regulate gene expression. Here we present the crystal structures of BRI1(LRR) in free and brassinolide-bound forms. BRI1(LRR) exists as a monomer in crystals and solution independent of brassinolide. It comprises a helical solenoid structure that accommodates a separate insertion domain at its concave surface. Sandwiched between them, brassinolide binds to a hydrophobicity-dominating surface groove on BRI1(LRR). Brassinolide recognition by BRI1(LRR) is through an induced-fit mechanism involving stabilization of two interdomain loops that creates a pronounced non-polar surface groove for the hormone binding. Together, our results define the molecular mechanisms by which BRI1 recognizes brassinosteroids and provide insight into brassinosteroid-induced BRI1 activation.     

A study on the Web intelligence

This paper surveys important aspects of Web Intelligence (WI). WI explores the fundamental roles as well as practical impacts of Artificial Intelligence (AI) and advanced Information Technology (IT) on the next generation of Web - related products, systens, and activities. As a direction for scientific research and devlopment,WI can be extremely beneficial for the field of Artificial Intelligence in Education (AIED). This paper covers these issues only very briefly. It focuses more on other issues in WI, such as intelligent Web services, and semantic web, and proposes how to use them as basis for tackling new and challenging research problems in AIED.     

Genome shuffling leads to rapid phenotypic improvement in bacteria

For millennia, selective breeding, on the basis of biparental mating, has led to the successful improvement of plants and animals to meet societal needs. At a molecular level, DNA shuffling mimics, yet accelerates, evolutionary processes, and allows the breeding and improvement of individual genes and subgenomic DNA fragments. We describe here whole-genome shuffling; a process that combines the advantage of multi-parental crossing allowed by DNA shuffling with the recombination of entire genomes normally associated with conventional breeding. We show that recursive genomic recombination within a population of bacteria can efficiently generate combinatorial libraries of new strains. When applied to a population of phenotypically selected bacteria, many of these new strains show marked improvements in the selected phenotype. We demonstrate the use of this approach through the rapid improvement of tylosin production from Streptomyces fradiae. This approach has the potential to facilitate cell and metabolic engineering and provide a non-recombinant alternative to the rapid production of improved organisms.     

Voltage-sensor activation with a tarantula toxin as cargo

The opening and closing of voltage-activated Na+, Ca2+ and K+ (Kv) channels underlies electrical and chemical signalling throughout biology, yet the structural basis of voltage sensing is unknown. Hanatoxin is a tarantula toxin that inhibits Kv channels by binding to voltage-sensor paddles, crucial helix-turn-helix motifs within the voltage-sensing domains that are composed of S3b and S4 helices. The active surface of the toxin is amphipathic, and related toxins have been shown to partition into membranes, raising the possibility that the toxin is concentrated in the membrane and interacts only weakly and transiently with the voltage sensors. Here we examine the kinetics and state dependence of the toxin-channel interaction and the physical location of the toxin in the membrane. We find that hanatoxin forms a strong and stable complex with the voltage sensors, far outlasting fluctuations of the voltage sensors between resting (closed) conformations at negative voltages and activated (open) conformations at positive voltages. Toxin affinity is reduced by voltage-sensor activation, explaining why the toxin stabilizes the resting conformation. We also find that when hanatoxin partitions into membranes it is localized to an interfacial region, with Trp 30 positioned about 8.5 A from the centre of the bilayer. These results demonstrate that voltage-sensor paddles activate with a toxin as cargo, and suggest that the paddles traverse no more than the outer half of the bilayer during activation.     

Antiinflammatory and analgesic effect of herbal cocktail Hongbaekjeong via inhibition of proinflammatory cytokines and prostaglandin E2 release

Though Hongbaekjeong(HBJ),a hebal mixture of three medicinal plants,has been traditionally used for arthritis and muscular pain,its scientific evidence still remains unclear.Thus,in the present study,analgesic and anti-inflammatory mechanism of HBJ was evaluated in vitro and in vivo.HBJ significantly reduced NO production and prostaglandin E2(PGE2)release and also attenuated the expression of cyclooxygenase 2(COX-2)in lipopolysaccharides(LPS)and interferon(IFN)-c treated RAW 264.7 cells.Furthermore,HBJ abrogated the production of proinflammatory cytokines such as interleukin(IL)1b,IL-6,IL-8 and monocyte chemoattractant protein-1(MCP-1)in LPS and IFN-c treated RAW 264.7 cells.In addition,HBJ significantly decreased the number of writhing syndrome induced by acetic acid,and also increased latency in hot-plate method and tail flick test in mice.Consistently,HBJ significantly reduced the edema volume in the hind paw of the rats with arthritis induced by Freund’s complete adjuvant(FCA)compared to untreated control.Collectively,our findings demonstrate the antiinflammatory and analgesic potential of HBJ via inhibition of proinflammatory cytokines and PGE2 release for treatment of arthritis and muscular pain.