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A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera 总被引:1,自引:0,他引:1
James C Ugo V Le Couédic JP Staerk J Delhommeau F Lacout C Garçon L Raslova H Berger R Bennaceur-Griscelli A Villeval JL Constantinescu SN Casadevall N Vainchenker W 《Nature》2005,434(7037):1144-1148
Myeloproliferative disorders are clonal haematopoietic stem cell malignancies characterized by independency or hypersensitivity of haematopoietic progenitors to numerous cytokines. The molecular basis of most myeloproliferative disorders is unknown. On the basis of the model of chronic myeloid leukaemia, it is expected that a constitutive tyrosine kinase activity could be at the origin of these diseases. Polycythaemia vera is an acquired myeloproliferative disorder, characterized by the presence of polycythaemia diversely associated with thrombocytosis, leukocytosis and splenomegaly. Polycythaemia vera progenitors are hypersensitive to erythropoietin and other cytokines. Here, we describe a clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients. The mutation, a valine-to-phenylalanine substitution at amino acid position 617, leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and induces erythrocytosis in a mouse model. As this mutation is also found in other myeloproliferative disorders, this unique mutation will permit a new molecular classification of these disorders and novel therapeutical approaches. 相似文献
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Independent records of relative magnetic palaeointensity from sediment cores in different areas of the world can be stacked together to extract the evolution of the geomagnetic dipole moment and thus provide information regarding the processes governing the geodynamo. So far, this procedure has been limited to the past 800,000 years (800 kyr; ref. 3), which does not include any geomagnetic reversals. Here we present a composite curve that shows the evolution of the dipole moment during the past two million years. This reconstruction is in good agreement with the absolute dipole moments derived from volcanic lavas, which were used for calibration. We show that, at least during this period, the time-averaged field was higher during periods without reversals but the amplitude of the short-term oscillations remained the same. As a consequence, few intervals of very low intensity, and thus fewer instabilities, are expected during periods with a strong average dipole moment, whereas more excursions and reversals are expected during periods of weak field intensity. We also observe that the axial dipole begins to decay 60-80 kyr before reversals, but rebuilds itself in the opposite direction in only a few thousand years. 相似文献
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The fungal glutathione S-transferase system. Evidence of new classes in the wood-degrading basidiomycete Phanerochaete chrysosporium 总被引:1,自引:0,他引:1
Mélanie Morel Andrew A. Ngadin Michel Droux Jean-Pierre Jacquot Eric Gelhaye 《Cellular and molecular life sciences : CMLS》2009,66(23):3711-3725
The recent release of several basidiomycete genome sequences allows an improvement of the classification of fungal glutathione S-transferases (GSTs). GSTs are well-known detoxification enzymes which can catalyze the conjugation of glutathione to non-polar compounds that contain an electrophilic carbon, nitrogen, or sulfur atom. Following this mechanism, they are able to metabolize drugs, pesticides, and many other xenobiotics and peroxides. A genomic and phylogenetic analysis of GST classes in various sequenced fungi—zygomycetes, ascomycetes, and basidiomycetes—revealed some particularities in GST distribution, in comparison with previous analyses with ascomycetes only. By focusing essentially on the wood-degrading basidiomycete Phanerochaete chrysosporium, this analysis highlighted a new fungal GST class named GTE, which is related to bacterial etherases, and two new subclasses of the omega class GSTs. Moreover, our phylogenetic analysis suggests a relationship between the saprophytic behavior of some fungi and the number and distribution of some GST isoforms within specific classes. 相似文献
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1 Results No doubt that one of the major breakthroughs in polymer chemistry was the discovery and the progressive implementation of the “living“ and “controlled“ polymerizations.These now widely used techniques allow not only to control with an extreme precision the molar masses and their distributions but also to synthesise easily a broad variety of architectures from block and graft copolymers,miktoarms stars,to polymer brushes,hyperbranched polymers,dendrimers,etc....They opened an immense domain of ... 相似文献
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Langevin Y Douté S Vincendon M Poulet F Bibring JP Gondet B Schmitt B Forget F 《Nature》2006,442(7104):790-792
The seasonal polar ice caps of Mars are composed mainly of CO2 ice. A region of low (< 30%) albedo has been observed within the south seasonal cap during early to mid-spring. The low temperature of this 'cryptic region' has been attributed to a clear slab of nearly pure CO2 ice, with the low albedo resulting from absorption by the underlying surface. Here we report near-infrared imaging spectroscopy of the south seasonal cap. The deep and broad CO2 absorption bands that are expected in the near-infrared with a thick transparent slab of CO2 ice are not observed. Models of the observed spectra indicate that the low albedo results from extensive dust contamination close to the surface of a CO2 ice layer, which could be linked to atmospheric circulation patterns. The strength of the CO2 absorption increases after mid-spring, so part of the dust is either carried away or buried more deeply in the ice layer during the CO2 ice sublimation process. 相似文献
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Evolution is based on genetic variability and subsequent phenotypic selection. Mechanisms that modulate the rate of mutation according to environmental cues, and thus control the balance between genetic stability and flexibility, might provide a distinct evolutionary advantage. Stress-induced mutations stimulated by unfavorable environments, and possible mechanisms for their induction, have been described for several organisms, but research in this area has mainly focused on microorganisms. We have analyzed the influence of adverse environmental conditions on the genetic stability of the higher plant Arabidopsis thaliana. Here we show that a biotic stress factor-attack by the oomycete pathogen Peronospora parasitica-can stimulate somatic recombination in Arabidopsis. The same effect was observed when plant pathogen-defense mechanisms were activated by the chemicals 2,6-dichloroisonicotinic acid (INA) or benzothiadiazole (BTH), or by a mutation (cim3). Together with previous studies of recombination induced by abiotic factors, these findings suggest that increased somatic recombination is a general stress response in plants. The increased genetic flexibility might facilitate evolutionary adaptation of plant populations to stressful environments. 相似文献
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The only naturally occurring isotope of bismuth, 209Bi, is commonly regarded as the heaviest stable isotope. But like most other heavy nuclei abundant in nature and characterized by an exceptionally long lifetime, it is metastable with respect to alpha-decay. However, the decay usually evades observation because the nuclear structure of 209Bi gives rise to an extremely low decay probability and, moreover, generates low-energy alpha-particles difficult to detect. Indeed, dedicated experiments attempting to record the alpha-decay of 209Bi in nuclear emulsions failed. However, scintillating bolometers operated at temperatures below 100 mK offer improved detection efficiency and sensitivity, whereas a broad palette of targets could be available. Here we report the successful use of this method for the unambiguous detection of 209Bi alpha-decay in bismuth germanate detectors cooled to 20 mK. We measure an energy release of 3,137 +/- 1 (statistical) +/- 2 (systematic) keV and a half-life of (1.9 +/- 0.2) x 10(19) yr, which are in agreement with expected values. 相似文献
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