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31.
Giardine B Borg J Higgs DR Peterson KR Philipsen S Maglott D Singleton BK Anstee DJ Basak AN Clark B Costa FC Faustino P Fedosyuk H Felice AE Francina A Galanello R Gallivan MV Georgitsi M Gibbons RJ Giordano PC Harteveld CL Hoyer JD Jarvis M Joly P Kanavakis E Kollia P Menzel S Miller W Moradkhani K Old J Papachatzopoulou A Papadakis MN Papadopoulos P Pavlovic S Perseu L Radmilovic M Riemer C Satta S Schrijver I Stojiljkovic M Thein SL Traeger-Synodinos J Tully R Wada T Waye JS Wiemann C 《Nature genetics》2011,43(4):295-301
We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases. 相似文献
32.
Schizophrenia is an etiologically heterogeneous psychiatric disease, which exists in familial and nonfamilial (sporadic) forms. Here, we examine the possibility that rare de novo copy number (CN) mutations with relatively high penetrance contribute to the genetic component of schizophrenia. We carried out a whole-genome scan and implemented a number of steps for finding and confirming CN mutations. Confirmed de novo mutations were significantly associated with schizophrenia (P = 0.00078) and were collectively approximately 8 times more frequent in sporadic (but not familial) cases with schizophrenia than in unaffected controls. In comparison, rare inherited CN mutations were only modestly enriched in sporadic cases. Our results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease. 相似文献
33.
Pravenec M Churchill PC Churchill MC Viklicky O Kazdova L Aitman TJ Petretto E Hubner N Wallace CA Zimdahl H Zidek V Landa V Dunbar J Bidani A Griffin K Qi N Maxova M Kren V Mlejnek P Wang J Kurtz TW 《Nature genetics》2008,40(8):952-954
To identify renally expressed genes that influence risk for hypertension, we integrated expression quantitative trait locus (QTL) analysis of the kidney with genome-wide correlation analysis of renal expression profiles and blood pressure in recombinant inbred strains derived from the spontaneously hypertensive rat (SHR). This strategy, together with renal transplantation studies in SHR progenitor, transgenic and congenic strains, identified deficient renal expression of Cd36 encoding fatty acid translocase as a genetically determined risk factor for spontaneous hypertension. 相似文献
34.
Joseph W. Dauben 《Archive for History of Exact Sciences》2008,62(2):91-178
In December and January of 1983–1984, archaeologists excavating the tomb of an ancient Chinese provincial bureaucrat at a
Western Han Dynasty site near Zhangjiashan, in Jiangling county, Hubei Province, discovered a number of books on bamboo strips,
including inter alia works on legal statutes, military practice, and medicine. Among these was a previously unknown mathematical work on some
200 bamboo strips, the
Suan shu shu, or Book of Numbers and Computations. Based upon other works found in the tomb, especially a copy of the
Er nian lü ling (Laws and Decrees of the Second Year (of the reign of empress Lü, i.e. Lü Hou)), archaeologists have dated the tomb to ca. 186 BCE (Lü Hou’s regency lasted from 188 to 180 BCE). The Suan shu shu, as the earliest yet discovered work devoted specifically to mathematics from ancient China, has stirred considerable interest
among Chinese historians of science. The translation and commentary offered here draw extensively on the works cited in Sect.
3 below. Several appendixes devoted to specific issues related to translating the Suan shu shu, including its title and the problem of determining English equivalents for various commodities that arise in the text, may
be found in Appendix II.
An erratum to this article can be found at 相似文献
35.
Recent experience with several high-profile drugs demonstrates the great challenges in developing effective and safe therapeutics. A complementary approach to the popular paradigm of disease genetics is based on inherited factors that reduce the incidence and severity of disease among individuals who are genetically predisposed to disease. We propose testing specifically for modifier genes and protective alleles among at-risk individuals and studying the efficacy of therapeutics based on the genetics of health. 相似文献
36.
The ergodic hierarchy, randomness and Hamiltonian chaos 总被引:1,自引:1,他引:1
Joseph Berkovitz Roman Frigg Fred Kronz 《Studies in History and Philosophy of Science Part B: Studies in History and Philosophy of Modern Physics》2006,37(4):661-691
Various processes are often classified as both deterministic and random or chaotic. The main difficulty in analysing the randomness of such processes is the apparent tension between the notions of randomness and determinism: what type of randomness could exist in a deterministic process? Ergodic theory seems to offer a particularly promising theoretical tool for tackling this problem by positing a hierarchy, the so-called ‘ergodic hierarchy’ (EH), which is commonly assumed to provide a hierarchy of increasing degrees of randomness. However, that notion of randomness requires clarification. The mathematical definition of EH does not make explicit appeal to randomness; nor does the usual way of presenting EH involve a specification of the notion of randomness that is supposed to underlie the hierarchy. In this paper we argue that EH is best understood as a hierarchy of random behaviour if randomness is explicated in terms of unpredictability. We then show that, contrary to common wisdom, EH is useful in characterising the behaviour of Hamiltonian dynamical systems. 相似文献
37.
Evolution can favour more than one reproductive tactic among conspecifics of the same sex. Under the conditional evolutionarily stable strategy, individuals adopt the tactic that generates the highest fitness return for their status: large males guard females, whereas small males sneak copulations. Tactics change at the status at which fitness benefits switch from favouring one tactic to favouring the alternative. This 'switchpoint' is expressed in many species as a threshold between divergent morphologies. Environmental and demographic parameters that influence the relative fitness of male tactics are predicted to determine a population's switchpoint and consequently whether the population is monomorphic or dimorphic. Here we show threshold evolution in the forceps dimorphism of the European earwig Forficula auricularia and document the transition from completely monomorphic to classical male-dimorphic populations over a distance of only 40 km. Because the superior fighting ability of the dominant morph will be more frequently rewarded at high encounter rates, population density is likely to be a key determinant of the relative fitness of the alternative tactics, and consequently the threshold. We show that, as predicted, population density correlates strongly with the shift in threshold, and that this factor drives the local evolution of the male dimorphism in these island populations. Our data provide evidence for the origin of phenotypic diversity within populations, through the evolution of a switchpoint in a conditional strategy that has responded to local population density. 相似文献
38.
39.
Abrescia NG Cockburn JJ Grimes JM Sutton GC Diprose JM Butcher SJ Fuller SD San Martín C Burnett RM Stuart DI Bamford DH Bamford JK 《Nature》2004,432(7013):68-74
The structure of the membrane-containing bacteriophage PRD1 has been determined by X-ray crystallography at about 4 A resolution. Here we describe the structure and location of proteins P3, P16, P30 and P31. Different structural proteins seem to have specialist roles in controlling virus assembly. The linearly extended P30 appears to nucleate the formation of the icosahedral facets (composed of trimers of the major capsid protein, P3) and acts as a molecular tape-measure, defining the size of the virus and cementing the facets together. Pentamers of P31 form the vertex base, interlocking with subunits of P3 and interacting with the membrane protein P16. The architectural similarities with adenovirus and one of the largest known virus particles PBCV-1 support the notion that the mechanism of assembly of PRD1 is scaleable and applies across the major viral lineage formed by these viruses. 相似文献
40.
Cockburn JJ Abrescia NG Grimes JM Sutton GC Diprose JM Benevides JM Thomas GJ Bamford JK Bamford DH Stuart DI 《Nature》2004,432(7013):122-125
Membranes are essential for selectively controlling the passage of molecules in and out of cells and mediating the response of cells to their environment. Biological membranes and their associated proteins present considerable difficulties for structural analysis. Although enveloped viruses have been imaged at about 9 A resolution by cryo-electron microscopy and image reconstruction, no detailed crystallographic structure of a membrane system has been described. The structure of the bacteriophage PRD1 particle, determined by X-ray crystallography at about 4 A resolution, allows the first detailed analysis of a membrane-containing virus. The architecture of the viral capsid and its implications for virus assembly are presented in the accompanying paper. Here we show that the electron density also reveals the icosahedral lipid bilayer, beneath the protein capsid, enveloping the viral DNA. The viral membrane contains about 26,000 lipid molecules asymmetrically distributed between the membrane leaflets. The inner leaflet is composed predominantly of zwitterionic phosphatidylethanolamine molecules, facilitating a very close interaction with the viral DNA, which we estimate to be packaged to a pressure of about 45 atm, factors that are likely to be important during membrane-mediated DNA translocation into the host cell. In contrast, the outer leaflet is enriched in phosphatidylglycerol and cardiolipin, which show a marked lateral segregation within the icosahedral asymmetric unit. In addition, the lipid headgroups show a surprising degree of order. 相似文献