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761.
Tschöp M Castañeda TR Joost HG Thöne-Reineke C Ortmann S Klaus S Hagan MM Chandler PC Oswald KD Benoit SC Seeley RJ Kinzig KP Moran TH Beck-sickinger AG Koglin N Rodgers RJ Blundell JE Ishii Y Beattie AH Holch P Allison DB Raun K Madsen K Wulff BS Stidsen CE Birringer M Kreuzer OJ Schindler M Arndt K Rudolf K Mark M Deng XY Whitcomb DC Halem H Taylor J Dong J Datta R Culler M Craney S Flora D Smiley D Heiman ML Withcomb DC 《Nature》2004,430(6996):1 p following 165; discussion 2 p following 165
Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36. 相似文献
762.
The formation of glasses is normal for substances that remain liquid over a wide temperature range (the 'good glassformers') and can be induced for most liquids if cooling is fast enough to bypass crystallization. During reheating but still below the melting point, good glassformers exhibit glass transitions as they abruptly transform into supercooled liquids, whereas other substances transform directly from the glassy to the crystalline state. Whether water exhibits a glass transition before crystallization has been much debated over five decades. For the last 20 years, the existence of a glass transition at 136 K (ref. 3) has been widely accepted, but the transition exhibits qualities difficult to reconcile with our current knowledge of glass transitions. Here we report detailed calorimetric characterizations of hyperquenched inorganic glasses that, when heated, do not crystallize before reaching their glass transition temperatures. We compare our results to the behaviour of glassy water and find that small endothermic effects, such as the one attributed to the glass transition of water, are only a 'shadow' of the real glass transition occurring at higher temperatures, thus substantiating the conclusion that the glass transition of water cannot be probed directly. 相似文献
763.
High-quality electron beams from a laser wakefield accelerator using plasma-channel guiding 总被引:2,自引:0,他引:2
Geddes CG Toth CS Van Tilborg J Esarey E Schroeder CB Bruhwiler D Nieter C Cary J Leemans WP 《Nature》2004,431(7008):538-541
Laser-driven accelerators, in which particles are accelerated by the electric field of a plasma wave (the wakefield) driven by an intense laser, have demonstrated accelerating electric fields of hundreds of GV m(-1) (refs 1-3). These fields are thousands of times greater than those achievable in conventional radio-frequency accelerators, spurring interest in laser accelerators as compact next-generation sources of energetic electrons and radiation. To date, however, acceleration distances have been severely limited by the lack of a controllable method for extending the propagation distance of the focused laser pulse. The ensuing short acceleration distance results in low-energy beams with 100 per cent electron energy spread, which limits potential applications. Here we demonstrate a laser accelerator that produces electron beams with an energy spread of a few per cent, low emittance and increased energy (more than 10(9) electrons above 80 MeV). Our technique involves the use of a preformed plasma density channel to guide a relativistically intense laser, resulting in a longer propagation distance. The results open the way for compact and tunable high-brightness sources of electrons and radiation. 相似文献
764.
Late Cenozoic terrestrial fossil records of North America are biased by a predominance of mid-latitude deposits, mostly in the western half of the continent. Consequently, the biological history of eastern North America, including the eastern deciduous forest, remains largely hidden. Unfortunately, vertebrate fossil sites from this vast region are rare, and few pertain to the critically important late Tertiary period, during which intensified global climatic changes took place. Moreover, strong phylogenetic affinities between the flora of eastern North America and eastern Asia clearly demonstrate formerly contiguous connections, but disparity among shared genera (eastern Asia-eastern North America disjunction) implies significant periods of separation since at least the Miocene epoch. Lacustrine sediments deposited within a former sinkhole in the southern Appalachian Mountains provide a rare example of a late Miocene to early Pliocene terrestrial biota from a forested ecosystem. Here we show that the vertebrate remains contained within this deposit represent a unique combination of North American and Eurasian taxa. A new genus and species of the red (lesser) panda (Pristinailurus bristoli), the earliest and most primitive so far known, was recovered. Also among the fauna are a new species of Eurasian badger (Arctomeles dimolodontus) and the largest concentration of fossil tapirs ever recorded. Cladistical analyses of the two new carnivores strongly suggest immigration events that were earlier than and distinct from previous records, and that the close faunal affinities between eastern North America and eastern Asia in the late Tertiary period are consistent with the contemporaneous botanical record. 相似文献
765.
New evidence on the earliest human presence at high northern latitudes in northeast Asia 总被引:1,自引:0,他引:1
Zhu RX Potts R Xie F Hoffman KA Deng CL Shi CD Pan YX Wang HQ Shi RP Wang YC Shi GH Wu NQ 《Nature》2004,431(7008):559-562
The timing of early human dispersal to Asia is a central issue in the study of human evolution. Excavations in predominantly lacustrine sediments at Majuangou, Nihewan basin, north China, uncovered four layers of indisputable hominin stone tools. Here we report magnetostratigraphic results that constrain the age of the four artefact layers to an interval of nearly 340,000 yr between the Olduvai subchron and the Cobb Mountain event. The lowest layer, about 1.66 million years old (Myr), provides the oldest record of stone-tool processing of animal tissues in east Asia. The highest layer, at about 1.32 Myr, correlates with the stone tool layer at Xiaochangliang, previously considered the oldest archaeological site in this region. The findings at Majuangou indicate that the oldest known human presence in northeast Asia at 40 degrees N is only slightly younger than that in western Asia. This result implies that a long yet rapid migration from Africa, possibly initiated during a phase of warm climate, enabled early human populations to inhabit northern latitudes of east Asia over a prolonged period. 相似文献
766.
The tripartite cytolethal distending toxin (CDT) induces cell cycle arrest and apoptosis in eukaryotic cells. The subunits CdtA and CdtC associate with the nuclease CdtB to form a holotoxin that translocates CdtB into the host cell, where it acts as a genotoxin by creating DNA lesions. Here we show that the crystal structure of the holotoxin from Haemophilus ducreyi reveals that CDT consists of an enzyme of the DNase-I family, bound to two ricin-like lectin domains. CdtA, CdtB and CdtC form a ternary complex with three interdependent molecular interfaces, characterized by globular, as well as extensive non-globular, interactions. The lectin subunits form a deeply grooved, highly aromatic surface that we show to be critical for toxicity. The holotoxin possesses a steric block of the CdtB active site by means of a non-globular extension of the CdtC subunit, and we identify putative DNA binding residues in CdtB that are essential for toxin activity. 相似文献
767.
Deloukas P Earthrowl ME Grafham DV Rubenfield M French L Steward CA Sims SK Jones MC Searle S Scott C Howe K Hunt SE Andrews TD Gilbert JG Swarbreck D Ashurst JL Taylor A Battles J Bird CP Ainscough R Almeida JP Ashwell RI Ambrose KD Babbage AK Bagguley CL Bailey J Banerjee R Bates K Beasley H Bray-Allen S Brown AJ Brown JY Burford DC Burrill W Burton J Cahill P Camire D Carter NP Chapman JC Clark SY Clarke G Clee CM Clegg S Corby N Coulson A Dhami P Dutta I Dunn M Faulkner L Frankish A 《Nature》2004,429(6990):375-381
768.
Under conditions of tissue injury, myocardial replication and regeneration have been reported. A growing number of investigators have implicated adult bone marrow (BM) in this process, suggesting that marrow serves as a reservoir for cardiac precursor cells. It remains unclear which BM cell(s) can contribute to myocardium, and whether they do so by transdifferentiation or cell fusion. Here, we studied the ability of c-kit-enriched BM cells, Lin- c-kit+ BM cells and c-kit+ Thy1.1(lo) Lin- Sca-1+ long-term reconstituting haematopoietic stem cells to regenerate myocardium in an infarct model. Cells were isolated from transgenic mice expressing green fluorescent protein (GFP) and injected directly into ischaemic myocardium of wild-type mice. Abundant GFP+ cells were detected in the myocardium after 10 days, but by 30 days, few cells were detectable. These GFP+ cells did not express cardiac tissue-specific markers, but rather, most of them expressed the haematopoietic marker CD45 and myeloid marker Gr-1. We also studied the role of circulating cells in the repair of ischaemic myocardium using GFP+-GFP- parabiotic mice. Again, we found no evidence of myocardial regeneration from blood-borne partner-derived cells. Our data suggest that even in the microenvironment of the injured heart, c-kit-enriched BM cells, Lin- c-kit+ BM cells and c-kit+ Thy1.1(lo) Lin- Sca-1+ long-term reconstituting haematopoietic stem cells adopt only traditional haematopoietic fates. 相似文献
769.
770.