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International Consortium for Blood Pressure Genome-Wide Association Studies Ehret GB Munroe PB Rice KM Bochud M Johnson AD Chasman DI Smith AV Tobin MD Verwoert GC Hwang SJ Pihur V Vollenweider P O'Reilly PF Amin N Bragg-Gresham JL Teumer A Glazer NL Launer L Zhao JH Aulchenko Y Heath S Sõber S Parsa A Luan J Arora P Dehghan A Zhang F Lucas G Hicks AA Jackson AU Peden JF Tanaka T Wild SH Rudan I Igl W Milaneschi Y Parker AN Fava C Chambers JC Fox ER Kumari M Go MJ van der Harst P Kao WH 《Nature》2011,478(7367):103-109
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. 相似文献
83.
Kharchenko PV Alekseyenko AA Schwartz YB Minoda A Riddle NC Ernst J Sabo PJ Larschan E Gorchakov AA Gu T Linder-Basso D Plachetka A Shanower G Tolstorukov MY Luquette LJ Xi R Jung YL Park RW Bishop EP Canfield TK Sandstrom R Thurman RE MacAlpine DM Stamatoyannopoulos JA Kellis M Elgin SC Kuroda MI Pirrotta V Karpen GH Park PJ 《Nature》2011,471(7339):480-485
Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function. 相似文献
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Timoney N Baumgart I Johanning M Varón AF Plenio MB Retzker A Wunderlich Ch 《Nature》2011,476(7359):185-188
Trapped atomic ions have been used successfully to demonstrate basic elements of universal quantum information processing. Nevertheless, scaling up such methods to achieve large-scale, universal quantum information processing (or more specialized quantum simulations) remains challenging. The use of easily controllable and stable microwave sources, rather than complex laser systems, could remove obstacles to scalability. However, the microwave approach has drawbacks: it involves the use of magnetic-field-sensitive states, which shorten coherence times considerably, and requires large, stable magnetic field gradients. Here we show how to overcome both problems by using stationary atomic quantum states as qubits that are induced by microwave fields (that is, by dressing magnetic-field-sensitive states with microwave fields). This permits fast quantum logic, even in the presence of a small (effective) Lamb-Dicke parameter (and, therefore, moderate magnetic field gradients). We experimentally demonstrate the basic building blocks of this scheme, showing that the dressed states are long lived and that coherence times are increased by more than two orders of magnitude relative to those of bare magnetic-field-sensitive states. This improves the prospects of microwave-driven ion trap quantum information processing, and offers a route to extending coherence times in all systems that suffer from magnetic noise, such as neutral atoms, nitrogen-vacancy centres, quantum dots or circuit quantum electrodynamic systems. 相似文献
85.
Bos KI Schuenemann VJ Golding GB Burbano HA Waglechner N Coombes BK McPhee JB DeWitte SN Meyer M Schmedes S Wood J Earn DJ Herring DA Bauer P Poinar HN Krause J 《Nature》2011,478(7370):506-510
Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections. 相似文献
86.
Cerling TE Wynn JG Andanje SA Bird MI Korir DK Levin NE Mace W Macharia AN Quade J Remien CH 《Nature》2011,476(7358):51-56
The role of African savannahs in the evolution of early hominins has been debated for nearly a century. Resolution of this issue has been hindered by difficulty in quantifying the fraction of woody cover in the fossil record. Here we show that the fraction of woody cover in tropical ecosystems can be quantified using stable carbon isotopes in soils. Furthermore, we use fossil soils from hominin sites in the Awash and Omo-Turkana basins in eastern Africa to reconstruct the fraction of woody cover since the Late Miocene epoch (about 7 million years ago). (13)C/(12)C ratio data from 1,300 palaeosols at or adjacent to hominin sites dating to at least 6 million years ago show that woody cover was predominantly less than ~40% at most sites. These data point to the prevalence of open environments at the majority of hominin fossil sites in eastern Africa over the past 6 million years. 相似文献
87.
Radu I Vahaplar K Stamm C Kachel T Pontius N Dürr HA Ostler TA Barker J Evans RF Chantrell RW Tsukamoto A Itoh A Kirilyuk A Rasing T Kimel AV 《Nature》2011,472(7342):205-208
Ferromagnetic or antiferromagnetic spin ordering is governed by the exchange interaction, the strongest force in magnetism. Understanding spin dynamics in magnetic materials is an issue of crucial importance for progress in information processing and recording technology. Usually the dynamics are studied by observing the collective response of exchange-coupled spins, that is, spin resonances, after an external perturbation by a pulse of magnetic field, current or light. The periods of the corresponding resonances range from one nanosecond for ferromagnets down to one picosecond for antiferromagnets. However, virtually nothing is known about the behaviour of spins in a magnetic material after being excited on a timescale faster than that corresponding to the exchange interaction (10-100?fs), that is, in a non-adiabatic way. Here we use the element-specific technique X-ray magnetic circular dichroism to study spin reversal in GdFeCo that is optically excited on a timescale pertinent to the characteristic time of the exchange interaction between Gd and Fe spins. We unexpectedly find that the ultrafast spin reversal in this material, where spins are coupled antiferromagnetically, occurs by way of a transient ferromagnetic-like state. Following the optical excitation, the net magnetizations of the Gd and Fe sublattices rapidly collapse, switch their direction and rebuild their net magnetic moments at substantially different timescales; the net magnetic moment of the Gd sublattice is found to reverse within 1.5 picoseconds, which is substantially slower than the Fe reversal time of 300 femtoseconds. Consequently, a transient state characterized by a temporary parallel alignment of the net Gd and Fe moments emerges, despite their ground-state antiferromagnetic coupling. These surprising observations, supported by atomistic simulations, provide a concept for the possibility of manipulating magnetic order on the timescale of the exchange interaction. 相似文献
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