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11.
Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice 总被引:48,自引:0,他引:48
Cockayne DA Hamilton SG Zhu QM Dunn PM Zhong Y Novakovic S Malmberg AB Cain G Berson A Kassotakis L Hedley L Lachnit WG Burnstock G McMahon SB Ford AP 《Nature》2000,407(6807):1011-1015
Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density. Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder. 相似文献
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Doppler spectroscopy has detected 152 planets around nearby stars. A major puzzle is why many of their orbits are highly eccentric; all planets in our Solar System are on nearly circular orbits, as is expected if they formed by accretion processes in a protostellar disk. Several mechanisms have been proposed to generate large eccentricities after planet formation, but so far there has been little observational evidence to support any particular model. Here we report that the current orbital configuration of the three giant planets around upsilon Andromedae (upsilon And) probably results from a close dynamical interaction with another planet, now lost from the system. The planets started on nearly circular orbits, but chaotic evolution caused the outer planet (upsilon And d) to be perturbed suddenly into a higher-eccentricity orbit. The coupled evolution of the system then causes slow periodic variations in the eccentricity of the middle planet (upsilon And c). Indeed, we show that upsilon And c periodically returns to a very nearly circular state every 6,700 years. 相似文献
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Miley GK Overzier RA Tsvetanov ZI Bouwens RJ Benítez N Blakeslee JP Ford HC Illingworth GD Postman M Rosati P Clampin M Hartig GF Zirm AW Röttgering HJ Venemans BP Ardila DR Bartko F Broadhurst TJ Brown RA Burrows CJ Cheng ES Cross NJ De Breuck C Feldman PD Franx M Golimowski DA Gronwall C Infante L Martel AR Menanteau F Meurer GR Sirianni M Kimble RA Krist JE Sparks WB Tran HD White RL Zheng W 《Nature》2004,427(6969):47-50
The most massive galaxies and the richest clusters are believed to have emerged from regions with the largest enhancements of mass density relative to the surrounding space. Distant radio galaxies may pinpoint the locations of the ancestors of rich clusters, because they are massive systems associated with 'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen. A powerful technique for detecting high-redshift galaxies is to search for the characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by the intervening intergalactic medium. Here we report multicolour imaging of the most distant candidate protocluster, TN J1338-1942 at a redshift z approximately 4.1. We find a large number of objects with the characteristic colours of galaxies at that redshift, and we show that this excess is concentrated around the targeted dominant radio galaxy. Our data therefore indicate that TN J1338-1942 is indeed the most distant cluster progenitor of a rich local cluster, and that galaxy clusters began forming when the Universe was only ten per cent of its present age. 相似文献
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Ford CB Lin PL Chase MR Shah RR Iartchouk O Galagan J Mohaideen N Ioerger TR Sacchettini JC Lipsitch M Flynn JL Fortune SM 《Nature genetics》2011,43(5):482-486
Tuberculosis poses a global health emergency, which has been compounded by the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains. We used whole-genome sequencing to compare the accumulation of mutations in Mtb isolated from cynomolgus macaques with active, latent or reactivated disease. We sequenced 33 Mtb isolates from nine macaques with an average genome coverage of 93% and an average read depth of 117×. Based on the distribution of SNPs observed, we calculated the mutation rates for these disease states. We found a similar mutation rate during latency as during active disease or in a logarithmically growing culture over the same period of time. The pattern of polymorphisms suggests that the mutational burden in vivo is because of oxidative DNA damage. We show that Mtb continues to acquire mutations during disease latency, which may explain why isoniazid monotherapy for latent tuberculosis is a risk factor for the emergence of isoniazid resistance. 相似文献
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信息化已经成为体育赛事播报时,提升信息传播及时性、实时性的必然手段。体育赛事成绩信息系统是赛事信息化的重要组成部分,主要研究我省体育赛事成绩信息系统功能构架,提出关键技术解决方案,结合第十七届省运会应用案例,展望系统开发方向及应用前景。 相似文献
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