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871.
We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining a receptor displacement analysis, both opiate alkaloids displaced [3H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again suggesting that a novel mu opiate receptor may be present. Received 1 November 2001; received after revision 1 February 2002; accepted 1 February 2002  相似文献   
872.
Microbial cycling of volatile organic sulfur compounds   总被引:7,自引:0,他引:7  
Microbial cycling of volatile organic sulfur compounds (VOSCs), especially dimethyl sulfide (DMS) and methanethiol (MT), is intensively studied because these compounds play an important role in the processes of global warming, acid precipitation, and the global sulfur cycle. VOSC concentrations in freshwater sediments are low due to the balance between the formation and degradation of these compounds. These reactions occur for the greater part at the oxic/anoxic interphase of sediment and water column. In contrast to marine ecosystems, where dimethylsulfoniopropionate is the main precursor of MT and DMS, in freshwater ecosystems, VOSCs are formed mainly by methylation of sulfide and to a lesser extent from the degradation of S-containing amino acids. One of the major routes for DMS and MT formation through sulfide methylation is anaerobic O-demethylation of methoxylated aromatic compounds. Inhibition studies have revealed that the major part of the endogenously produced MT and DMS is degraded anaerobically by methanogens. The major bacterial groups involved in formation and consumption of VOSCs are described.  相似文献   
873.
Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.  相似文献   
874.
Intense radiation from lasers has opened up many new areas of research in physics and chemistry, and has revolutionized optical technology. So far, most work in the field of nonlinear processes has been restricted to infrared, visible and ultraviolet light, although progress in the development of X-ray lasers has been made recently. With the advent of a free-electron laser in the soft-X-ray regime below 100 nm wavelength, a new light source is now available for experiments with intense, short-wavelength radiation that could be used to obtain deeper insights into the structure of matter. Other free-electron sources with even shorter wavelengths are planned for the future. Here we present initial results from a study of the interaction of soft X-ray radiation, generated by a free-electron laser, with Xe atoms and clusters. We find that, whereas Xe atoms become only singly ionized by the absorption of single photons, absorption in clusters is strongly enhanced. On average, each atom in large clusters absorbs up to 400 eV, corresponding to 30 photons. We suggest that the clusters are heated up and electrons are emitted after acquiring sufficient energy. The clusters finally disintegrate completely by Coulomb explosion.  相似文献   
875.
Buckling A  Rainey PB 《Nature》2002,420(6915):496-499
Exploiters (parasites and predators) are thought to play a significant role in diversification, and ultimately speciation, of their hosts or prey. Exploiters may drive sympatric (within-population) diversification if there are a variety of exploiter-resistance strategies or fitness costs associated with exploiter resistance. Exploiters may also drive allopatric (between-population) diversification by creating different selection pressures and increasing the rate of random divergence. We examined the effect of a virulent viral parasite (phage) on the diversification of the bacterium Pseudomonas fluorescens in spatially structured microcosms. Here we show that in the absence of phages, bacteria rapidly diversified into spatial niche specialists with similar patterns of diversity across replicate populations. In the presence of phages, sympatric diversity was greatly reduced, as a result of phage-imposed reductions in host density decreasing competition for resources. In contrast, allopatric diversity was greatly increased as a result of phage-imposed selection for resistance, which caused populations to follow divergent evolutionary trajectories. These results show that exploiters can drive diversification between populations, but may inhibit diversification within populations by opposing diversifying selection that arises from resource competition.  相似文献   
876.
The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes.  相似文献   
877.
Inflammation and therapeutic vaccination in CNS diseases   总被引:20,自引:0,他引:20  
Weiner HL  Selkoe DJ 《Nature》2002,420(6917):879-884
The spectrum of inflammatory diseases of the central nervous system has been steadily expanding from classical autoimmune disorders such as multiple sclerosis to far more diverse diseases. Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches. The notion of 'vaccinating' individuals against a neurodegenerative disorder such as Alzheimer's disease is a marked departure from classical thinking about mechanism and treatment, and yet therapeutic vaccines for both Alzheimer's disease and multiple sclerosis have been validated in animal models and are in the clinic. Such approaches, however, have the potential to induce unwanted inflammatory responses as well as to provide benefit.  相似文献   
878.
879.
Respiration in the open ocean   总被引:11,自引:0,他引:11  
del Giorgio PA  Duarte CM 《Nature》2002,420(6914):379-384
A key question when trying to understand the global carbon cycle is whether the oceans are net sources or sinks of carbon. This will depend on the production of organic matter relative to the decomposition due to biological respiration. Estimates of respiration are available for the top layers, the mesopelagic layer, and the abyssal waters and sediments of various ocean regions. Although the total open ocean respiration is uncertain, it is probably substantially greater than most current estimates of particulate organic matter production. Nevertheless, whether the biota act as a net source or sink of carbon remains an open question.  相似文献   
880.
Transport of calcium ions across membranes and against a thermodynamic gradient is essential to many biological processes, including muscle contraction, the citric acid cycle, glycogen metabolism, release of neurotransmitters, vision, biological signal transduction and immune response. Synthetic systems that transport metal ions across lipid or liquid membranes are well known, and in some cases light has been used to facilitate transport. Typically, a carrier molecule located in a symmetric membrane binds the ion from aqueous solution on one side and releases it on the other. The thermodynamic driving force is provided by an ion concentration difference between the two aqueous solutions, coupling to such a gradient in an auxiliary species, or photomodulation of the carrier by an asymmetric photon flux. Here we report a different approach, in which active transport is driven not by concentration gradients, but by light-induced electron transfer in a photoactive molecule that is asymmetrically disposed across a lipid bilayer. The system comprises a synthetic, light-driven transmembrane Ca2+ pump based on a redox-sensitive, lipophilic Ca2+-binding shuttle molecule whose function is powered by an intramembrane artificial photosynthetic reaction centre. The resulting structure transports calcium ions across the bilayer of a liposome to develop both a calcium ion concentration gradient and a membrane potential, expanding Mitchell's concept of a redox loop mechanism for protons to include divalent cations. Although the quantum yield is relatively low (approximately 1 per cent), the Ca2+ electrochemical potential developed is significant.  相似文献   
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