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121.
Analysis of one million base pairs of Neanderthal DNA 总被引:1,自引:0,他引:1
Green RE Krause J Ptak SE Briggs AW Ronan MT Simons JF Du L Egholm M Rothberg JM Paunovic M Pääbo S 《Nature》2006,444(7117):330-336
Neanderthals are the extinct hominid group most closely related to contemporary humans, so their genome offers a unique opportunity to identify genetic changes specific to anatomically fully modern humans. We have identified a 38,000-year-old Neanderthal fossil that is exceptionally free of contamination from modern human DNA. Direct high-throughput sequencing of a DNA extract from this fossil has thus far yielded over one million base pairs of hominoid nuclear DNA sequences. Comparison with the human and chimpanzee genomes reveals that modern human and Neanderthal DNA sequences diverged on average about 500,000 years ago. Existing technology and fossil resources are now sufficient to initiate a Neanderthal genome-sequencing effort. 相似文献
122.
A principle that has emerged from studies of protein aggregation is that proteins typically can misfold into a range of different aggregated forms. Moreover, the phenotypic and pathological consequences of protein aggregation depend critically on the specific misfolded form. A striking example of this is the prion strain phenomenon, in which prion particles composed of the same protein cause distinct heritable states. Accumulating evidence from yeast prions such as [PSI+] and mammalian prions argues that differences in the prion conformation underlie prion strain variants. Nonetheless, it remains poorly understood why changes in the conformation of misfolded proteins alter their physiological effects. Here we present and experimentally validate an analytical model describing how [PSI+] strain phenotypes arise from the dynamic interaction among the effects of prion dilution, competition for a limited pool of soluble protein, and conformation-dependent differences in prion growth and division rates. Analysis of three distinct prion conformations of yeast Sup35 (the [PSI+] protein determinant) and their in vivo phenotypes reveals that the Sup35 amyloid causing the strongest phenotype surprisingly shows the slowest growth. This slow growth, however, is more than compensated for by an increased brittleness that promotes prion division. The propensity of aggregates to undergo breakage, thereby generating new seeds, probably represents a key determinant of their physiological impact for both infectious (prion) and non-infectious amyloids. 相似文献
123.
Nusbaum C Mikkelsen TS Zody MC Asakawa S Taudien S Garber M Kodira CD Schueler MG Shimizu A Whittaker CA Chang JL Cuomo CA Dewar K FitzGerald MG Yang X Allen NR Anderson S Asakawa T Blechschmidt K Bloom T Borowsky ML Butler J Cook A Corum B DeArellano K DeCaprio D Dooley KT Dorris L Engels R Glöckner G Hafez N Hagopian DS Hall JL Ishikawa SK Jaffe DB Kamat A Kudoh J Lehmann R Lokitsang T Macdonald P Major JE Matthews CD Mauceli E Menzel U Mihalev AH Minoshima S Murayama Y Naylor JW Nicol R 《Nature》2006,439(7074):331-335
The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution. 相似文献
124.
Over the past decade, diagnostic classification models (DCMs) have become an active area of psychometric research. Despite their use, the reliability of examinee estimates in DCM applications has seldom been reported. In this paper, a reliability measure for the categorical latent variables of DCMs is defined. Using theory-and simulation-based results, we show how DCMs uniformly provide greater examinee estimate reliability than IRT models for tests of the same length, a result that is a consequence of the smaller range of latent variable values examinee estimates can take in DCMs. We demonstrate this result by comparing DCM and IRT reliability for a series of models estimated with data from an end-of-grade test, culminating with a discussion of how DCMs can be used to change the character of large scale testing, either by shortening tests that measure examinees unidimensionally or by providing more reliable multidimensional measurement for tests of the same length. 相似文献
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Votier SC Furness RW Bearhop S Crane JE Caldow RW Catry P Ensor K Hamer KC Hudson AV Kalmbach E Klomp NI Pfeiffer S Phillips RA Prieto I Thompson DR 《Nature》2004,427(6976):727-730
It is clear that discards from commercial fisheries are a key food resource for many seabird species around the world. But predicting the response of seabird communities to changes in discard rates is problematic and requires historical data to elucidate the confounding effects of other, more 'natural' ecological processes. In the North Sea, declining stocks, changes in technical measures, changes in population structure and the establishment of a recovery programme for cod (Gadus morhua) will alter the amount of fish discarded. This region also supports internationally important populations of seabirds, some of which feed extensively, but facultatively, on discards, in particular on undersized haddock (Melanogrammus aeglefinus) and whiting (Merlangius merlangus). Here we use long-term data sets from the northern North Sea to show that there is a direct link between discard availability and discard use by a generalist predator and scavenger--the great skua (Stercorarius skua). Reduced rates of discarding, particularly when coupled with reduced availability of small shoaling pelagic fish such as sandeel (Ammodytes marinus), result in an increase in predation by great skuas on other birds. This switching of prey by a facultative scavenger presents a potentially serious threat to some seabird communities. 相似文献
128.
The overall extent of habitat use by leatherback turtles in the North Atlantic, and hence their possible interactions with longline fisheries, is unknown. Here we use long-term satellite telemetry to reveal that leatherbacks range throughout the North Atlantic, indicating that closing limited areas to longline fisheries will probably have only partial success in reducing turtle bycatch. Although turtles dive very deeply on occasion (one descended to a maximum depth of 1,230 metres, which represents the deepest dive ever recorded for a reptile), they generally restrict their diving to less than 250 metres, which increases the chance that they will encounter longline hooks. 相似文献
129.
130.
Yalcin B Willis-Owen SA Fullerton J Meesaq A Deacon RM Rawlins JN Copley RR Morris AP Flint J Mott R 《Nature genetics》2004,36(11):1197-1202
Here we present a strategy to determine the genetic basis of variance in complex phenotypes that arise from natural, as opposed to induced, genetic variation in mice. We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing anxiety. We also show that this locus can be subdivided into three regions, one of which contains Rgs2, which encodes a regulator of G protein signaling. We then use quantitative complementation to show that Rgs2 is a quantitative trait gene. This combined genetic and functional approach should be applicable to the analysis of any quantitative trait. 相似文献