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.     

ORGANIZATIONAL LEARNING AND VENDOR SUPPORT QUALITY BY THE USAGE OF APPLICATION SOFTWARE PACKAGES： A STUDY OF ASIAN ENTREPRENEURS

In this paper we study how organizational learning impacts organizational behavior, and howvendor support quality enhances product adoption and usage behavior.These constructs were verifiedusing Application Software Packages(ASP)-a prewritten, precoded, commercially available set ofprograms that eliminates the need for individuals or organizations to write their own softwareprograms for certain functions. The relationship between ASP usage, usage outcomes and useprocesses were also investigated. Two hundred and ninety-five Chinese, Indian, and Malayentrepreneurships were studied. It was found that usage outcome strongly determines usage, while useprocess has only an indirect relationship (via outcome) on usage. The impact of organizational learningand vendor service quality on usage, usage outcome, and use process were robust. Theoretical andpractical implications of the research are discussed.     

Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2

TET2 is a close relative of TET1, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. The gene encoding TET2 resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies. Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML). We show here that TET2 mutations associated with myeloid malignancies compromise catalytic activity. Bone marrow samples from patients with TET2 mutations displayed uniformly low levels of 5hmC in genomic DNA compared to bone marrow samples from healthy controls. Moreover, small hairpin RNA (shRNA)-mediated depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte/macrophage lineages in culture. There was no significant difference in DNA methylation between bone marrow samples from patients with high 5hmC versus healthy controls, but samples from patients with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites. Our results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis. Measurement of 5hmC levels in myeloid malignancies may prove valuable as a diagnostic and prognostic tool, to tailor therapies and assess responses to anticancer drugs.     

Semi-annual oscillations in Saturn's low-latitude stratospheric temperatures

Observations of oscillations of temperature and wind in planetary atmospheres provide a means of generalizing models for atmospheric dynamics in a diverse set of planets in the Solar System and elsewhere. An equatorial oscillation similar to one in the Earth's atmosphere has been discovered in Jupiter. Here we report the existence of similar oscillations in Saturn's atmosphere, from an analysis of over two decades of spatially resolved observations of its 7.8-microm methane and 12.2-microm ethane stratospheric emissions, where we compare zonal-mean stratospheric brightness temperatures at planetographic latitudes of 3.6 degrees and 15.5 degrees in both the northern and the southern hemispheres. These results support the interpretation of vertical and meridional variability of temperatures in Saturn's stratosphere as a manifestation of a wave phenomenon similar to that on the Earth and in Jupiter. The period of this oscillation is 14.8 +/- 1.2 terrestrial years, roughly half of Saturn's year, suggesting the influence of seasonal forcing, as is the case with the Earth's semi-annual oscillation.     

Diseases associated with Juniperus osteosperma and a model for predicting their occurrence with environmental site factors

On 17 Utah juniper ( Juniperus osteosperma [Torrey] L.) sites studied in Utah, Gymnosporangium inconspicuum was the most common rust fungus, followed in frequency and severity by G. nelsoni, G. kernianum, and G. speciosum . The incidence of G. kernianum was correlated with moderate temperatures and greater than average precipitation. True mistletoe, Phoradendron juniperinum Engelm., was present on seven sites. Incidence of foliage diseases of the mold-mildew type was low on sites with low spring and summer temperatures and high on sites with high summer and fall precipitation. Wood rot was common, and incidence seemed to be correlated with low winter temperatures and low soil nitrate but not with annual precipitation. Needle blight, shoot dieback, and needle cast symptoms were common and considered of abiotic origin. Their nonparasitic nature was indicated by lack of association with pathogenic organisms and the positive correlation of their incidence with winter injury and summer drought factors. Needle blight was also positively correlated with high soil salinity but negatively with high soil calcium regardless of salinity. A nonparametric model was developed that accurately predicted the frequency of the mold-mildew type diseases of J. osteosperma based on measured environmental site factors.