Spider toxins activate the capsaicin receptor to produce inflammatory pain

Bites and stings from venomous creatures can produce pain and inflammation as part of their defensive strategy to ward off predators or competitors. Molecules accounting for lethal effects of venoms have been extensively characterized, but less is known about the mechanisms by which they produce pain. Venoms from spiders, snakes, cone snails or scorpions contain a pharmacopoeia of peptide toxins that block receptor or channel activation as a means of producing shock, paralysis or death. We examined whether these venoms also contain toxins that activate (rather than inhibit) excitatory channels on somatosensory neurons to produce a noxious sensation in mammals. Here we show that venom from a tarantula that is native to the West Indies contains three inhibitor cysteine knot (ICK) peptides that target the capsaicin receptor (TRPV1), an excitatory channel expressed by sensory neurons of the pain pathway. In contrast with the predominant role of ICK toxins as channel inhibitors, these previously unknown 'vanillotoxins' function as TRPV1 agonists, providing new tools for understanding mechanisms of TRP channel gating. Some vanillotoxins also inhibit voltage-gated potassium channels, supporting potential similarities between TRP and voltage-gated channel structures. TRP channels can now be included among the targets of peptide toxins, showing that animals, like plants (for example, chilli peppers), avert predators by activating TRP channels on sensory nerve fibres to elicit pain and inflammation.     

A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors

The amyloid proteins isolated from neuritic plaques and the cerebrovasculature of Alzheimer's disease are self-aggregating moieties termed A4 protein and beta-protein, respectively. A putative A4 amyloid precursor (herein termed A4(695] has been characterized by analysis of a human brain complementary DNA. We report here the sequence of a closely related amyloid cDNA, A4(751), distinguished from A4(695) by the presence of a 168 base-pair (bp) sequence which adds 57 amino acids to, and removes one residue from, the predicted A4(695) protein. The peptide predicted from this insert is very similar to the Kunitz family of serine proteinase inhibitors. The two A4-specific messenger RNAs are differentially expressed: in a limited survey, A4(751) mRNA appears to be ubiquitous, whereas A4(695) mRNA has a restricted pattern of expression which includes cells from neuronal tissue. These data may have significant implications for understanding amyloid deposition in Alzheimer's disease.     

A role for VEGF as a negative regulator of pericyte function and vessel maturation

Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) through their cognate receptors on endothelial cells and vascular smooth muscle cells (VSMCs), respectively. PDGF induces neovascularization by priming VSMCs/pericytes to release pro-angiogenic mediators. Although VEGF directly stimulates endothelial cell proliferation and migration, its role in pericyte biology is less clear. Here we define a role for VEGF as an inhibitor of neovascularization on the basis of its capacity to disrupt VSMC function. Specifically, under conditions of PDGF-mediated angiogenesis, VEGF ablates pericyte coverage of nascent vascular sprouts, leading to vessel destabilization. At the molecular level, VEGF-mediated activation of VEGF-R2 suppresses PDGF-Rbeta signalling in VSMCs through the assembly of a previously undescribed receptor complex consisting of PDGF-Rbeta and VEGF-R2. Inhibition of VEGF-R2 not only prevents assembly of this receptor complex but also restores angiogenesis in tissues exposed to both VEGF and PDGF. Finally, genetic deletion of tumour cell VEGF disrupts PDGF-Rbeta/VEGF-R2 complex formation and increases tumour vessel maturation. These findings underscore the importance of VSMCs/pericytes in neovascularization and reveal a dichotomous role for VEGF and VEGF-R2 signalling as both a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation.     

皮纳图博火山喷发物在南极点雪层内的记录及其意义

１９９１年６月菲律宾皮纳图博火山喷发,导致大气圈火山灰气溶胶含量激增,连同１９９１年８月智利哈德森火山喷发释放的火山灰一道,导致自１９９１年１２月起南极点降水中ＳＯ＾２－４开始增加,激光雷达同时也观测到富含火山微尘气团的到达。雪样中火山微粒的电镜分析结果,以及据物质平衡观测值估算的年代等表明,１９９４年１２月在南极点０．１－０．９ｍ雪层中可钭２次火山喷发事件区别开采、估算出南极点处皮纳图博火山和哈     

The genome sequence of the filamentous fungus Neurospora crassa

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes--more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca2+ signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes.     

Eruptions arising from tidally controlled periodic openings of rifts on Enceladus

In 2005, plumes were detected near the south polar region of Enceladus, a small icy satellite of Saturn. Observations of the south pole revealed large rifts in the crust, informally called 'tiger stripes', which exhibit higher temperatures than the surrounding terrain and are probably sources of the observed eruptions. Models of the ultimate interior source for the eruptions are under consideration. Other models of an expanding plume require eruptions from discrete sources, as well as less voluminous eruptions from a more extended source, to match the observations. No physical mechanism that matches the observations has been identified to control these eruptions. Here we report a mechanism in which temporal variations in tidal stress open and close the tiger-stripe rifts, governing the timing of eruptions. During each orbit, every portion of each tiger stripe rift spends about half the time in tension, which allows the rift to open, exposing volatiles, and allowing eruptions. In a complementary process, periodic shear stress along the rifts also generates heat along their lengths, which has the capacity to enhance eruptions. Plume activity is expected to vary periodically, affecting the injection of material into Saturn's E ring and its formation, evolution and structure. Moreover, the stresses controlling eruptions imply that Enceladus' icy shell behaves as a thin elastic layer, perhaps only a few tens of kilometres thick.     

Expression, purification and characterization of the soluble CuA domain of cytochrome c oxidase ofParacoccus versutus

The key subunit Ⅱ of cytochrome c oxidase (CcO) contains a soluble binuclear copper center (Cu_A) domain. The Cu_A domain of Paracoccus versutus was cloned, expressed, purified and characterized. The gene encoding the Cu_A domain in pET11d vector was expressed in E. coli BL21 (DE3). The results showed that the Cu_A domain was expressed mostly in inclusion bodies and the Cu_A domain protein synthesized in E. coli cells represents approximately 10 percent of the total cellular proteins. Dissolved in urea, dialyzed and recombined with Cu⁺/Cu²⁺ and purified by the Q-sepharose fast flow anion-exchange column and Sephadex G-75 gel filtration column, the soluble purple-colored protein, which shows a single band in electrophoresis, was obtained. The UV-visible absorption spectrum of Cu_A domain showed that there are intense band at 478 nm and a shoulder peak at 530 nm, and two weak bands at 360 and 806 nm respectively, which can be assigned to the charge transfer and the interactions of obitals of Cu—S and Cu——Cu in the mixed-valence binuclear metal center (Cu₂S₂R₂). The far-UV CD spectrum indicated that this domain is predominantly in β-sheet structure. The fluorescence spectra showed that its maximal excitation wavelength and maximal emission wavelength are at 280 and 345 nm, respectively.