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161.
Estimating the impact of school closure on influenza transmission from Sentinel data 总被引:1,自引:0,他引:1
The threat posed by the highly pathogenic H5N1 influenza virus requires public health authorities to prepare for a human pandemic. Although pre-pandemic vaccines and antiviral drugs might significantly reduce illness rates, their stockpiling is too expensive to be practical for many countries. Consequently, alternative control strategies, based on non-pharmaceutical interventions, are a potentially attractive policy option. School closure is the measure most often considered. The high social and economic costs of closing schools for months make it an expensive and therefore controversial policy, and the current absence of quantitative data on the role of schools during influenza epidemics means there is little consensus on the probable effectiveness of school closure in reducing the impact of a pandemic. Here, from the joint analysis of surveillance data and holiday timing in France, we quantify the role of schools in influenza epidemics and predict the effect of school closure during a pandemic. We show that holidays lead to a 20-29% reduction in the rate at which influenza is transmitted to children, but that they have no detectable effect on the contact patterns of adults. Holidays prevent 16-18% of seasonal influenza cases (18-21% in children). By extrapolation, we find that prolonged school closure during a pandemic might reduce the cumulative number of cases by 13-17% (18-23% in children) and peak attack rates by up to 39-45% (47-52% in children). The impact of school closure would be reduced if it proved difficult to maintain low contact rates among children for a prolonged period. 相似文献
162.
Carlton JM Adams JH Silva JC Bidwell SL Lorenzi H Caler E Crabtree J Angiuoli SV Merino EF Amedeo P Cheng Q Coulson RM Crabb BS Del Portillo HA Essien K Feldblyum TV Fernandez-Becerra C Gilson PR Gueye AH Guo X Kang'a S Kooij TW Korsinczky M Meyer EV Nene V Paulsen I White O Ralph SA Ren Q Sargeant TJ Salzberg SL Stoeckert CJ Sullivan SA Yamamoto MM Hoffman SL Wortman JR Gardner MJ Galinski MR Barnwell JW Fraser-Liggett CM 《Nature》2008,455(7214):757-763
The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species. 相似文献
163.
Thorgeirsson TE Geller F Sulem P Rafnar T Wiste A Magnusson KP Manolescu A Thorleifsson G Stefansson H Ingason A Stacey SN Bergthorsson JT Thorlacius S Gudmundsson J Jonsson T Jakobsdottir M Saemundsdottir J Olafsdottir O Gudmundsson LJ Bjornsdottir G Kristjansson K Skuladottir H Isaksson HJ Gudbjartsson T Jones GT Mueller T Gottsäter A Flex A Aben KK de Vegt F Mulders PF Isla D Vidal MJ Asin L Saez B Murillo L Blondal T Kolbeinsson H Stefansson JG Hansdottir I Runarsdottir V Pola R Lindblad B 《Nature》2008,452(7187):638-642
Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases. 相似文献
164.
The four-way (Holliday) DNA junction is the central intermediate in homologous recombination, a ubiquitous process that is important in DNA repair and generation of genetic diversity. The penultimate stage of recombination requires resolution of the DNA junction into nicked-duplex species by the action of a junction-resolving enzyme, examples of which have been identified in a wide variety of organisms. These enzymes are nucleases that are highly selective for the structure of branched DNA. The mechanism of this selectivity has, however, been unclear in the absence of structural data. Here we present the crystal structure of the junction-resolving enzyme phage T7 endonuclease I in complex with a synthetic four-way DNA junction. Although the enzyme is structure-selective, significant induced fit occurs in the interaction, with changes in the structure of both the protein and the junction. The dimeric enzyme presents two binding channels that contact the backbones of the junction's helical arms over seven nucleotides. These interactions effectively measure the relative orientations and positions of the arms of the junction, thereby ensuring that binding is selective for branched DNA that can achieve this geometry. 相似文献
165.
Evidence for the deep recycling of surficial materials through the Earth's mantle and their antiquity has long been sought to understand the role of subducting plates and plumes in mantle convection. Radiogenic isotope evidence for such recycling remains equivocal because the age and location of parent-daughter fractionation are not known. Conversely, while stable isotopes can provide irrefutable evidence for low-temperature fractionation, their range in most unaltered oceanic basalts is limited and the age of any variation is unconstrained. Here we show that delta(18)O ratios in basalts from the Azores are often lower than in pristine mantle. This, combined with increased Nb/B ratios and a large range in delta(11)B ratios, provides compelling evidence for the recycling of materials that had undergone fractionation near the Earth's surface. Moreover, delta(11)B is negatively correlated with (187)Os/(188)Os ratios, which extend to subchondritic values, constraining the age of the high Nb/B, (11)B-enriched endmember to be more than 2.5 billion years (Gyr) old. We infer this component to be melt- and fluid-depleted lithospheric mantle from a subducted oceanic plate, whereas other Azores basalts contain a contribution from approximately 3-Gyr-old melt-enriched basalt. We conclude that both components are most probably derived from an Archaean oceanic plate that was subducted, arguably into the deep mantle, where it was stored until thermal buoyancy caused it to rise beneath the Azores islands approximately 3 Gyr later. 相似文献
166.
167.
The accessible chromatin landscape of the human genome 总被引:2,自引:0,他引:2
RE Thurman E Rynes R Humbert J Vierstra MT Maurano E Haugen NC Sheffield AB Stergachis H Wang B Vernot K Garg S John R Sandstrom D Bates L Boatman TK Canfield M Diegel D Dunn AK Ebersol T Frum E Giste AK Johnson EM Johnson T Kutyavin B Lajoie BK Lee K Lee D London D Lotakis S Neph F Neri ED Nguyen H Qu AP Reynolds V Roach A Safi ME Sanchez A Sanyal A Shafer JM Simon L Song S Vong M Weaver Y Yan Z Zhang Z Zhang B Lenhard M Tewari MO Dorschner RS Hansen PA Navas G Stamatoyannopoulos VR Iyer 《Nature》2012,489(7414):75-82
168.
Shah SP Roth A Goya R Oloumi A Ha G Zhao Y Turashvili G Ding J Tse K Haffari G Bashashati A Prentice LM Khattra J Burleigh A Yap D Bernard V McPherson A Shumansky K Crisan A Giuliany R Heravi-Moussavi A Rosner J Lai D Birol I Varhol R Tam A Dhalla N Zeng T Ma K Chan SK Griffith M Moradian A Cheng SW Morin GB Watson P Gelmon K Chia S Chin SF Curtis C Rueda OM Pharoah PD Damaraju S Mackey J Hoon K Harkins T Tadigotla V Sigaroudinia M Gascard P Tlsty T Costello JF Meyer IM Eaves CJ Wasserman WW 《Nature》2012,486(7403):395-399
Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes. 相似文献
169.
Jones FC Grabherr MG Chan YF Russell P Mauceli E Johnson J Swofford R Pirun M Zody MC White S Birney E Searle S Schmutz J Grimwood J Dickson MC Myers RM Miller CT Summers BR Knecht AK Brady SD Zhang H Pollen AA Howes T Amemiya C;Broad Institute Genome Sequencing Platform & Whole Genome Assembly Team Baldwin J Bloom T Jaffe DB Nicol R Wilkinson J Lander ES Di Palma F Lindblad-Toh K Kingsley DM 《Nature》2012,484(7392):55-61
Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine-freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine-freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature. 相似文献
170.
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups 总被引:1,自引:0,他引:1
Curtis C Shah SP Chin SF Turashvili G Rueda OM Dunning MJ Speed D Lynch AG Samarajiwa S Yuan Y Gräf S Ha G Haffari G Bashashati A Russell R McKinney S;METABRIC Group Langerød A Green A Provenzano E Wishart G Pinder S Watson P Markowetz F Murphy L Ellis I Purushotham A Børresen-Dale AL Brenton JD Tavaré S Caldas C Aparicio S 《Nature》2012,486(7403):346-352