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221.
Genome-wide detection and characterization of positive selection in human populations 总被引:3,自引:0,他引:3
Sabeti PC Varilly P Fry B Lohmueller J Hostetter E Cotsapas C Xie X Byrne EH McCarroll SA Gaudet R Schaffner SF Lander ES;International HapMap Consortium Frazer KA Ballinger DG Cox DR Hinds DA Stuve LL Gibbs RA Belmont JW Boudreau A Hardenbol P Leal SM Pasternak S Wheeler DA Willis TD Yu F Yang H Zeng C Gao Y Hu H Hu W Li C Lin W Liu S Pan H Tang X Wang J Wang W Yu J Zhang B Zhang Q Zhao H Zhao H Zhou J Gabriel SB Barry R Blumenstiel B Camargo A Defelice M Faggart M Goyette M Gupta S Moore J 《Nature》2007,449(7164):913-918
With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia. 相似文献
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Non-volcanic tremor and low-frequency earthquake swarms 总被引:11,自引:0,他引:11
Non-volcanic tremor is a weak, extended duration seismic signal observed episodically on some major faults, often in conjunction with slow slip events. Such tremor may hold the key to understanding fundamental processes at the deep roots of faults, and could signal times of accelerated slip and hence increased seismic hazard. The mechanism underlying the generation of tremor and its relationship to aseismic slip are, however, as yet unresolved. Here we demonstrate that tremor beneath Shikoku, Japan, can be explained as a swarm of small, low-frequency earthquakes, each of which occurs as shear faulting on the subduction-zone plate interface. This suggests that tremor and slow slip are different manifestations of a single process. 相似文献
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Demonstration of controlled-NOT quantum gates on a pair of superconducting quantum bits 总被引:1,自引:0,他引:1
Quantum computation requires quantum logic gates that use the interaction within pairs of quantum bits (qubits) to perform conditional operations. Superconducting qubits may offer an attractive route towards scalable quantum computing. In previous experiments on coupled superconducting qubits, conditional gate behaviour and entanglement were demonstrated. Here we demonstrate selective execution of the complete set of four different controlled-NOT (CNOT) quantum logic gates, by applying microwave pulses of appropriate frequency to a single pair of coupled flux qubits. All two-qubit computational basis states and their superpositions are used as input, while two independent single-shot SQUID detectors measure the output state, including qubit-qubit correlations. We determined the gate's truth table by directly measuring the state transfer amplitudes and by acquiring the relevant quantum phase shift using a Ramsey-like interference experiment. The four conditional gates result from the symmetry of the qubits in the pair: either qubit can assume the role of control or target, and the gate action can be conditioned on either the 0-state or the 1-state. These gates are now sufficiently characterized to be used in quantum algorithms, and together form an efficient set of versatile building blocks. 相似文献
226.
Pandey UB Nie Z Batlevi Y McCray BA Ritson GP Nedelsky NB Schwartz SL DiProspero NA Knight MA Schuldiner O Padmanabhan R Hild M Berry DL Garza D Hubbert CC Yao TP Baehrecke EH Taylor JP 《Nature》2007,447(7146):859-863
A prominent feature of late-onset neurodegenerative diseases is accumulation of misfolded protein in vulnerable neurons. When levels of misfolded protein overwhelm degradative pathways, the result is cellular toxicity and neurodegeneration. Cellular mechanisms for degrading misfolded protein include the ubiquitin-proteasome system (UPS), the main non-lysosomal degradative pathway for ubiquitinated proteins, and autophagy, a lysosome-mediated degradative pathway. The UPS and autophagy have long been viewed as complementary degradation systems with no point of intersection. This view has been challenged by two observations suggesting an apparent interaction: impairment of the UPS induces autophagy in vitro, and conditional knockout of autophagy in the mouse brain leads to neurodegeneration with ubiquitin-positive pathology. It is not known whether autophagy is strictly a parallel degradation system, or whether it is a compensatory degradation system when the UPS is impaired; furthermore, if there is a compensatory interaction between these systems, the molecular link is not known. Here we show that autophagy acts as a compensatory degradation system when the UPS is impaired in Drosophila melanogaster, and that histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase that interacts with polyubiquitinated proteins, is an essential mechanistic link in this compensatory interaction. We found that compensatory autophagy was induced in response to mutations affecting the proteasome and in response to UPS impairment in a fly model of the neurodegenerative disease spinobulbar muscular atrophy. Autophagy compensated for impaired UPS function in an HDAC6-dependent manner. Furthermore, expression of HDAC6 was sufficient to rescue degeneration associated with UPS dysfunction in vivo in an autophagy-dependent manner. This study suggests that impairment of autophagy (for example, associated with ageing or genetic variation) might predispose to neurodegeneration. Morover, these findings suggest that it may be possible to intervene in neurodegeneration by augmenting HDAC6 to enhance autophagy. 相似文献
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228.
The upper atmospheres of the four Solar System giant planets exhibit high temperatures that cannot be explained by the absorption of sunlight. In the case of Saturn the temperatures predicted by models of solar heating are approximately 200 K, compared to temperatures of approximately 400 K observed independently in the polar regions and at 30 degrees latitude. This unexplained 'energy crisis' represents a major gap in our understanding of these planets' atmospheres. An important candidate for the source of the missing energy is the magnetosphere, which injects energy mostly in the polar regions of the planet. This polar energy input is believed to be sufficient to explain the observed temperatures, provided that it is efficiently redistributed globally by winds, a process that is not well understood. Here we show, using a numerical model, that the net effect of the winds driven by the polar energy inputs is not to heat but to cool the low-latitude thermosphere. This surprising result allows us to rule out known polar energy inputs as the solution to the energy crisis at Saturn. There is either an unknown--and large--source of polar energy, or, more probably, some other process heats low latitudes directly. 相似文献
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Most bony fishes rely on suction mechanisms to capture and transport prey. Once captured, prey are carried by water movement inside the oral cavity to a second set of jaws in the throat, the pharyngeal jaws, which manipulate the prey and assist in swallowing. Moray eels display much less effective suction-feeding abilities. Given this reduction in a feeding mechanism that is widespread and highly conserved in aquatic vertebrates, it is not known how moray eels swallow large fish and cephalopods. Here we show that the moray eel (Muraena retifera) overcomes reduced suction capacity by launching raptorial pharyngeal jaws out of its throat and into its oral cavity, where the jaws grasp the struggling prey animal and transport it back to the throat and into the oesophagus. This is the first described case of a vertebrate using a second set of jaws to both restrain and transport prey, and is the only alternative to the hydraulic prey transport reported in teleost fishes. The extreme mobility of the moray pharyngeal jaws is made possible by elongation of the muscles that control the jaws, coupled with reduction of adjacent gill-arch structures. The discovery that pharyngeal jaws can reach up from behind the skull to grasp prey in the oral jaws reveals a major innovation that may have contributed to the success of moray eels as apex predators hunting within the complex matrix of coral reefs. This alternative prey transport mode is mechanically similar to the ratcheting mechanisms used in snakes--a group of terrestrial vertebrates that share striking morphological, behavioural and ecological convergence with moray eels. 相似文献