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981.
Dopamine has been widely implicated as a mediator of many of the behavioural responses to drugs of abuse. To test the hypothesis that dopamine is an essential mediator of various opiate-induced responses, we administered morphine to mice unable to synthesize dopamine. We found that dopamine-deficient mice are unable to mount a normal locomotor response to morphine, but a small dopamine-independent increase in locomotion remains. Dopamine-deficient mice have a rightward shift in the dose-response curve to morphine on the tail-flick test (a pain sensitivity assay), suggesting either a decreased sensitivity to the analgesic effects of morphine and/or basal hyperalgesia. In contrast, dopamine-deficient mice display a robust conditioned place preference for morphine when given either caffeine or l-dihydroxyphenylalanine (a dopamine precursor that restores dopamine throughout the brain) during the testing phases. Together, these data demonstrate that dopamine is a crucial component of morphine-induced locomotion, dopamine may contribute to morphine analgesia, but that dopamine is not required for morphine-induced reward as measured by conditioned place preference. 相似文献
982.
Bacterial communities provide important services. They break down pollutants, municipal waste and ingested food, and they are the primary means by which organic matter is recycled to plants and other autotrophs. However, the processes that determine the rate at which these services are supplied are only starting to be identified. Biodiversity influences the way in which ecosystems function, but the form of the relationship between bacterial biodiversity and functioning remains poorly understood. Here we describe a manipulative experiment that measured how biodiversity affects the functioning of communities containing up to 72 bacterial species constructed from a collection of naturally occurring culturable bacteria. The experimental design allowed us to manipulate large numbers of bacterial species selected at random from those that were culturable. We demonstrate that there is a decelerating relationship between community respiration and increasing bacterial diversity. We also show that both synergistic interactions among bacterial species and the composition of the bacterial community are important in determining the level of ecosystem functioning. 相似文献
983.
Doping semiconductor nanocrystals 总被引:1,自引:0,他引:1
Doping--the intentional introduction of impurities into a material--is fundamental to controlling the properties of bulk semiconductors. This has stimulated similar efforts to dope semiconductor nanocrystals. Despite some successes, many of these efforts have failed, for reasons that remain unclear. For example, Mn can be incorporated into nanocrystals of CdS and ZnSe (refs 7-9), but not into CdSe (ref. 12)--despite comparable bulk solubilities of near 50 per cent. These difficulties, which have hindered development of new nanocrystalline materials, are often attributed to 'self-purification', an allegedly intrinsic mechanism whereby impurities are expelled. Here we show instead that the underlying mechanism that controls doping is the initial adsorption of impurities on the nanocrystal surface during growth. We find that adsorption--and therefore doping efficiency--is determined by three main factors: surface morphology, nanocrystal shape, and surfactants in the growth solution. Calculated Mn adsorption energies and equilibrium shapes for several nanocrystals lead to specific doping predictions. These are confirmed by measuring how the Mn concentration in ZnSe varies with nanocrystal size and shape. Finally, we use our predictions to incorporate Mn into previously undopable CdSe nanocrystals. This success establishes that earlier difficulties with doping are not intrinsic, and suggests that a variety of doped nanocrystals--for applications from solar cells to spintronics--can be anticipated. 相似文献
984.
Trace element signature of subduction-zone fluids, melts and supercritical liquids at 120-180 km depth 总被引:14,自引:0,他引:14
Fluids and melts liberated from subducting oceanic crust recycle lithophile elements back into the mantle wedge, facilitate melting and ultimately lead to prolific subduction-zone arc volcanism. The nature and composition of the mobile phases generated in the subducting slab at high pressures have, however, remained largely unknown. Here we report direct LA-ICPMS measurements of the composition of fluids and melts equilibrated with a basaltic eclogite at pressures equivalent to depths in the Earth of 120-180 km and temperatures of 700-1,200 degrees C. The resultant liquid/mineral partition coefficients constrain the recycling rates of key elements. The dichotomy of dehydration versus melting at 120 km depth is expressed through contrasting behaviour of many trace elements (U/Th, Sr, Ba, Be and the light rare-earth elements). At pressures equivalent to 180 km depth, however, a supercritical liquid with melt-like solubilities for the investigated trace elements is observed, even at low temperatures. This mobilizes most of the key trace elements (except the heavy rare-earth elements, Y and Sc) and thus limits fluid-phase transfer of geochemical signatures in subduction zones to pressures less than 6 GPa. 相似文献
985.
The anterior/posterior (A/P) and dorsal/ventral (D/V) compartment borders that subdivide the wing imaginal discs of Drosophila third instar larvae are each associated with a developmental organizer. Decapentaplegic (Dpp), a member of the transforming growth factor-beta (TGF-beta) superfamily, embodies the activity of the A/P organizer. It is produced at the A/P organizer and distributes in a gradient of decreasing concentration to regulate target genes, functioning non-autonomously to regulate growth and patterning of both the anterior and posterior compartments. Wingless (Wg) is produced at the D/V organizer and embodies its activity. The mechanisms that distribute Dpp and Wg are not known, but proposed mechanisms include extracellular diffusion, successive transfers between neighbouring cells, vesicle-mediated movement, and direct transfer via cytonemes. Cytonemes are actin-based filopodial extensions that have been found to orient towards the A/P organizer from outlying cells. Here we show that in the wing disc, cytonemes orient towards both the A/P and D/V organizers, and that their presence and orientation correlates with Dpp signalling. We also show that the Dpp receptor, Thickveins (Tkv), is present in punctae that move along cytonemes. These observations are consistent with a role for cytonemes in signal transduction. 相似文献
986.
Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways 总被引:21,自引:0,他引:21
Simons M Gloy J Ganner A Bullerkotte A Bashkurov M Krönig C Schermer B Benzing T Cabello OA Jenny A Mlodzik M Polok B Driever W Obara T Walz G 《Nature genetics》2005,37(5):537-543
Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development. 相似文献
987.
988.
Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer 总被引:25,自引:0,他引:25
Fraga MF Ballestar E Villar-Garea A Boix-Chornet M Espada J Schotta G Bonaldi T Haydon C Ropero S Petrie K Iyer NG Pérez-Rosado A Calvo E Lopez JA Cano A Calasanz MJ Colomer D Piris MA Ahn N Imhof A Caldas C Jenuwein T Esteller M 《Nature genetics》2005,37(4):391-400
CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells. 相似文献
989.
Mutations in SEPT9 cause hereditary neuralgic amyotrophy 总被引:7,自引:0,他引:7
Kuhlenbäumer G Hannibal MC Nelis E Schirmacher A Verpoorten N Meuleman J Watts GD De Vriendt E Young P Stögbauer F Halfter H Irobi J Goossens D Del-Favero J Betz BG Hor H Kurlemann G Bird TD Airaksinen E Mononen T Serradell AP Prats JM Van Broeckhoven C De Jonghe P Timmerman V Ringelstein EB Chance PF 《Nature genetics》2005,37(10):1044-1046
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis. 相似文献
990.
Remobilization of southern African desert dune systems by twenty-first century global warming 总被引:3,自引:0,他引:3
Although desert dunes cover 5 per cent of the global land surface and 30 per cent of Africa, the potential impacts of twenty-first century global warming on desert dune systems are not well understood. The inactive Sahel and southern African dune systems, which developed in multiple arid phases since the last interglacial period, are used today by pastoral and agricultural systems that could be disrupted if climate change alters twenty-first century dune dynamics. Empirical data and model simulations have established that the interplay between dune surface erodibility (determined by vegetation cover and moisture availability) and atmospheric erosivity (determined by wind energy) is critical for dunefield dynamics. This relationship between erodibility and erosivity is susceptible to climate-change impacts. Here we use simulations with three global climate models and a range of emission scenarios to assess the potential future activity of three Kalahari dunefields. We determine monthly values of dune activity by modifying and improving an established dune mobility index so that it can account for global climate model data outputs. We find that, regardless of the emission scenario used, significantly enhanced dune activity is simulated in the southern dunefield by 2039, and in the eastern and northern dunefields by 2069. By 2099 all dunefields are highly dynamic, from northern South Africa to Angola and Zambia. Our results suggest that dunefields are likely to be reactivated (the sand will become significantly exposed and move) as a consequence of twenty-first century climate warming. 相似文献