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31.
GIBBERELLIN INSENSITIVE DWARF1 encodes a soluble receptor for gibberellin   总被引:14,自引:0,他引:14  
Gibberellins (GAs) are phytohormones that are essential for many developmental processes in plants. It has been postulated that plants have both membrane-bound and soluble GA receptors; however, no GA receptors have yet been identified. Here we report the isolation and characterization of a new GA-insensitive dwarf mutant of rice, gid1. The GID1 gene encodes an unknown protein with similarity to the hormone-sensitive lipases, and we observed preferential localization of a GID1-green fluorescent protein (GFP) signal in nuclei. Recombinant glutathione S-transferase (GST)-GID1 had a high affinity only for biologically active GAs, whereas mutated GST-GID1 corresponding to three gid1 alleles had no GA-binding affinity. The dissociation constant for GA4 was estimated to be around 10(-7) M, enough to account for the GA dependency of shoot elongation. Moreover, GID1 bound to SLR1, a rice DELLA protein, in a GA-dependent manner in yeast cells. GID1 overexpression resulted in a GA-hypersensitive phenotype. Together, our results indicate that GID1 is a soluble receptor mediating GA signalling in rice.  相似文献   
32.
Coull JA  Beggs S  Boudreau D  Boivin D  Tsuda M  Inoue K  Gravel C  Salter MW  De Koninck Y 《Nature》2005,438(7070):1017-1021
Neuropathic pain that occurs after peripheral nerve injury depends on the hyperexcitability of neurons in the dorsal horn of the spinal cord. Spinal microglia stimulated by ATP contribute to tactile allodynia, a highly debilitating symptom of pain induced by nerve injury. Signalling between microglia and neurons is therefore an essential link in neuropathic pain transmission, but how this signalling occurs is unknown. Here we show that ATP-stimulated microglia cause a depolarizing shift in the anion reversal potential (E(anion)) in spinal lamina I neurons. This shift inverts the polarity of currents activated by GABA (gamma-amino butyric acid), as has been shown to occur after peripheral nerve injury. Applying brain-derived neurotrophic factor (BDNF) mimics the alteration in E(anion). Blocking signalling between BDNF and the receptor TrkB reverses the allodynia and the E(anion) shift that follows both nerve injury and administration of ATP-stimulated microglia. ATP stimulation evokes the release of BDNF from microglia. Preventing BDNF release from microglia by pretreating them with interfering RNA directed against BDNF before ATP stimulation also inhibits the effects of these cells on the withdrawal threshold and E(anion). Our results show that ATP-stimulated microglia signal to lamina I neurons, causing a collapse of their transmembrane anion gradient, and that BDNF is a crucial signalling molecule between microglia and neurons. Blocking this microglia-neuron signalling pathway may represent a therapeutic strategy for treating neuropathic pain.  相似文献   
33.
The human mind and body respond to stress, a state of perceived threat to homeostasis, by activating the sympathetic nervous system and secreting the catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response. The stress response is generally transient because its accompanying effects (for example, immunosuppression, growth inhibition and enhanced catabolism) can be harmful in the long term. When chronic, the stress response can be associated with disease symptoms such as peptic ulcers or cardiovascular disorders, and epidemiological studies strongly indicate that chronic stress leads to DNA damage. This stress-induced DNA damage may promote ageing, tumorigenesis, neuropsychiatric conditions and miscarriages. However, the mechanisms by which these DNA-damage events occur in response to stress are unknown. The stress hormone adrenaline stimulates β(2)-adrenoreceptors that are expressed throughout the body, including in germline cells and zygotic embryos. Activated β(2)-adrenoreceptors promote Gs-protein-dependent activation of protein kinase A (PKA), followed by the recruitment of β-arrestins, which desensitize G-protein signalling and function as signal transducers in their own right. Here we elucidate a molecular mechanism by which β-adrenergic catecholamines, acting through both Gs-PKA and β-arrestin-mediated signalling pathways, trigger DNA damage and suppress p53 levels respectively, thus synergistically leading to the accumulation of DNA damage. In mice and in human cell lines, β-arrestin-1 (ARRB1), activated via β(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold. Catecholamine-induced DNA damage is abrogated in Arrb1-knockout (Arrb1(-/-)) mice, which show preserved p53 levels in both the thymus, an organ that responds prominently to acute or chronic stress, and in the testes, in which paternal stress may affect the offspring's genome. Our results highlight the emerging role of ARRB1 as an E3-ligase adaptor in the nucleus, and reveal how DNA damage may accumulate in response to chronic stress.  相似文献   
34.
Thyrotrophin in the pars tuberalis triggers photoperiodic response   总被引:6,自引:0,他引:6  
Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) beta-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor-cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.  相似文献   
35.
Chenguodaite, approved by IMA-CNMMN (2004-042a), was discovered in the Bunan quartz vein-type gold deposit in the gold district of East Shandong Peninsula. The mineral occurs in high grade Au-Ag-Cu ores, coexisting with galena, chalcopyrite, hessite, electrum, unnamed Ag6TeS2 and AglsFeBiTe3Se, enclosed and replaced by native silver and acanthite. In the reflected light microscope, the mineral has light gray color, indistinguishable anistropism and hardness around 2-3. The color indices of chenguodaite relative to ICE C illuminator are: x=0.3027, y=0.3076, Y=25.78%,λd=474 nm, Pe=3.68%, similar to those of canfieldite. The average chemical composition from 16 microprobe analyses is Ag8.97Fe1.00Te1.99S4.04, idealized to AggFeTe2S4. The polycrystalline X-ray diffraction of chenguodaite by Gandolfi camera and synchrotron oscillation photography results in 67 reflections with the 12 strongest being (relative intensity in bracket): 6.742(69), 6.416(39), 5.951(33), 3.265(100), 2.981(24), 2.649(22), 2.25(24), 2.188(71), 2.142(22), 2.123(31), 2.044(23), 1.949(33), which are indexed to a primitive orthorhombic cell with a=12.769 (2) A, b= 14.814(2) A, c= 16.233 (1) A, V= 3070.6 A^3, Z= 9, Dcal.=6.85 g/cm^3. The name is for the late Prof. Chen Guoda, a famous Chinese geologist and the founder of Diwa-Geodepression theory of tectonics.  相似文献   
36.
Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.  相似文献   
37.
A phase transformation of a metastable Zr2Ni intermetallic crystalline phase to vitrify was studied with molecular dynamics (MD) simulations based on a plastic crystal model (PCM), which utilizes the orientational disorder of molecules of plastic crystals in a class of soft matter. The simulation results show ed that computational operations in MD-PCM for the random rotati ons of the clusters in the crystalline phase around their center of gravity and subsequent annealing lead to form a dense random pa cking structure from the metastable Zr2Ni phase. These randomly-rotated clusters provide high degrees of freedom in terms of atomic positions, which results in enhancing the glass-forming ability of the alloy. The critical fraction of the number of rotated cl usters for forming the glassy phase ( fcR) is evaluated to be 0.75 ? 0.80. Thus, the critical fraction of the number of un-rotated clusters (fcU=1?fcR) is close to the critical concentration of site percolation for metallic materials. The mechanism of the metastable Zr2Ni phase to vitrify with increasing fR was analyzed with a concept of communal entropy in the free volume theory with solid- and liquid-like cells proposed by Cohen and Grest. The MD-PCM for the metastable Zr2Ni phase suggests that Zr-based bulk metallic glass (BMG) can be regarded as an alloy in a high rotation entropy state of cl usters and that glass transition takes place by percolation of th e nuclei of a liquid-like glassy phase.  相似文献   
38.
The roots of most higher plants form arbuscular mycorrhiza, an ancient, phosphate-acquiring symbiosis with fungi, whereas only four related plant orders are able to engage in the evolutionary younger nitrogen-fixing root-nodule symbiosis with bacteria. Plant symbioses with bacteria and fungi require a set of common signal transduction components that redirect root cell development. Here we present two highly homologous genes from Lotus japonicus, CASTOR and POLLUX, that are indispensable for microbial admission into plant cells and act upstream of intracellular calcium spiking, one of the earliest plant responses to symbiotic stimulation. Surprisingly, both twin proteins are localized in the plastids of root cells, indicating a previously unrecognized role of this ancient endosymbiont in controlling intracellular symbioses that evolved more recently.  相似文献   
39.
Myelodysplastic syndromes and related disorders (myelodysplasia) are a heterogeneous group of myeloid neoplasms showing deregulated blood cell production with evidence of myeloid dysplasia and a predisposition to acute myeloid leukaemia, whose pathogenesis is only incompletely understood. Here we report whole-exome sequencing of 29 myelodysplasia specimens, which unexpectedly revealed novel pathway mutations involving multiple components of the RNA splicing machinery, including U2AF35, ZRSR2, SRSF2 and SF3B1. In a large series analysis, these splicing pathway mutations were frequent (~45 to ~85%) in, and highly specific to, myeloid neoplasms showing features of myelodysplasia. Conspicuously, most of the mutations, which occurred in a mutually exclusive manner, affected genes involved in the 3'-splice site recognition during pre-mRNA processing, inducing abnormal RNA splicing and compromised haematopoiesis. Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia.  相似文献   
40.
光敏色素影响赤霉素调控的水稻幼苗光形态建成特征   总被引:3,自引:0,他引:3  
赤霉素(gibberellin, GA)是一种重要的植物激素, 它与光敏色素协同调节拟南芥植株的光形态建成特征. 但是GA对水稻幼苗光形态建成和暗形态建成的影响, 特别是在此过程中光敏色素与GA之间的相互作用仍不清楚. 本研究利用野生型和光敏色素突变体(phyA和phyB)水稻作为研究材料, 分析了GA生物合成抑制剂多效唑(PAC)对黑暗和光照下生长的水稻幼苗胚芽鞘、地上部分和主根延伸以及光调控基因LHCB表达的影响. 据此推测, 在暗生长条件下, PAC处理能够抑制野生型水稻幼苗胚芽鞘的生长, 诱导LHCB基因的表达; phyA突变体对PAC处理的反应不如野生型敏感; phyB突变体和野生型反应基本相同. 在光照条件下, PAC处理能够抑制水稻幼苗地上部分的生长, phyB突变体对PAC处理的反应不如野生型和phyA突变体敏感. 此外, phyB介导的光信号负调控PAC诱导的主根延伸反应. 据此推测, GA是维持水稻幼苗暗形态建成、抑制光形态建成所必需的; 另一方面, phyA和phyB或正或负调控PAC所诱导的光形态建成反应. 本研究结果揭示了光敏色素和GA在水稻幼苗生长发育中的相互作用, 为进一步研究光和GA协同调控水稻发育的分子机制奠定了基础.  相似文献   
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