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Badano JL Leitch CC Ansley SJ May-Simera H Lawson S Lewis RA Beales PL Dietz HC Fisher S Katsanis N 《Nature》2006,439(7074):326-330
Epistatic interactions have an important role in phenotypic variability, yet the genetic dissection of such phenomena remains challenging. Here we report the identification of a novel locus, MGC1203, that contributes epistatic alleles to Bardet-Biedl syndrome (BBS), a pleiotropic, oligogenic disorder. MGC1203 encodes a pericentriolar protein that interacts and colocalizes with the BBS proteins. Sequencing of two independent BBS cohorts revealed a significant enrichment of a heterozygous C430T mutation in patients, and a transmission disequilibrium test (TDT) showed strong over-transmission of this variant. Further analyses showed that the 430T allele enhances the use of a cryptic splice acceptor site, causing the introduction of a premature termination codon (PTC) and the reduction of steady-state MGC1203 messenger RNA levels. Finally, recapitulation of the human genotypes in zebrafish shows that modest suppression of mgc1203 exerts an epistatic effect on the developmental phenotype of BBS morphants. Our data demonstrate how the combined use of biochemical, genetic and in vivo tools can facilitate the dissection of epistatic phenomena, and enhance our appreciation of the genetic basis of phenotypic variability. 相似文献
63.
Sebastian SE Harrison N Batista CD Balicas L Jaime M Sharma PA Kawashima N Fisher IR 《Nature》2006,441(7093):617-620
Competition between electronic ground states near a quantum critical point (QCP)--the location of a zero-temperature phase transition driven solely by quantum-mechanical fluctuations--is expected to lead to unconventional behaviour in low-dimensional systems. New electronic phases of matter have been predicted to occur in the vicinity of a QCP by two-dimensional theories, and explanations based on these ideas have been proposed for significant unsolved problems in condensed-matter physics, such as non-Fermi-liquid behaviour and high-temperature superconductivity. But the real materials to which these ideas have been applied are usually rendered three-dimensional by a finite electronic coupling between their component layers; a two-dimensional QCP has not been experimentally observed in any bulk three-dimensional system, and mechanisms for dimensional reduction have remained the subject of theoretical conjecture. Here we show evidence that the Bose-Einstein condensate of spin triplets in the three-dimensional Mott insulator BaCuSi2O6 (refs 12-16) provides an experimentally verifiable example of dimensional reduction at a QCP. The interplay of correlations on a geometrically frustrated lattice causes the individual two-dimensional layers of spin-(1/2) Cu2+ pairs (spin dimers) to become decoupled at the QCP, giving rise to a two-dimensional QCP characterized by linear power law scaling distinctly different from that of its three-dimensional counterpart. Thus the very notion of dimensionality can be said to acquire an 'emergent' nature: although the individual particles move on a three-dimensional lattice, their collective behaviour occurs in lower-dimensional space. 相似文献
64.
During the 1930s and 1940s, American physical organic chemists employed electronic theories of reaction mechanisms to construct models offering explanations of organic reactions. But two molecular rearrangements presented enormous challenges to model construction. The Claisen and Cope rearrangements were predominantly inaccessible to experimental investigation and they confounded explanation in theoretical terms. Drawing on the idea that models can be autonomous agents in the production of scientific knowledge, I argue that one group of models in particular were functionally autonomous from the Hughes–Ingold theory. Cope and Hardy’s models of the Claisen and Cope rearrangements were resources for the exploration of the Hughes–Ingold theory that otherwise lacked explanatory power. By generating ‘how-possibly’ explanations, these models explained how these rearrangements could happen rather than why they did happen. Furthermore, although these models were apparently closely connected to theory in terms of their construction, I argue that partial autonomy issued in extra-logical factors concerning the attitudes of American chemists to the Hughes–Ingold theory. And in the absence of a complete theoretical hegemony, a degree of consensus was reached concerning modelling the Claisen rearrangement mechanism. 相似文献
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非均匀光照下人脸眼睛的定位方法 总被引:4,自引:0,他引:4
考虑非均匀光照下人脸眼睛的检测问题,提出了一种利用高频信息模板匹配方法从复杂图像中定位人脸眼睛的方法。选取80幅光线较好的人脸图像,对它们做光线规范化,提取Gabor高频特征,构造模板。利用统计模式识别的原理,在眼睛的大致区域进行模板匹配,突出眉毛与眼睛这一整体的大致位置,然后进行二值投影,最终确定人眼的准确位置。大量实验表明,该算法具有很高的精度和很强的鲁棒性。 相似文献
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We investigated localities from which Eutamias atristriatus Bailey, 1913 (= Tamias minimus atristriatus ) and Zapus luteus Miller, 1911 (= Zapus hudsonius luteus ) were collected during a 1902 survey in the Sacramento Mountains, New Mexico, by the United States Biological Survey. The locality from which the holotype of Eutamias atristriatus was collected is restricted to James Canyon rather than the Rio Pe?asco. Locality records indicate that the historical distribution of Zapus hudsonius luteus and its obligate wetland habitat were broader than currently realized. 相似文献
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Emerging fungal threats to animal, plant and ecosystem health 总被引:7,自引:0,他引:7
Fisher MC Henk DA Briggs CJ Brownstein JS Madoff LC McCraw SL Gurr SJ 《Nature》2012,484(7393):186-194
The past two decades have seen an increasing number of virulent infectious diseases in natural populations and managed landscapes. In both animals and plants, an unprecedented number of fungal and fungal-like diseases have recently caused some of the most severe die-offs and extinctions ever witnessed in wild species, and are jeopardizing food security. Human activity is intensifying fungal disease dispersal by modifying natural environments and thus creating new opportunities for evolution. We argue that nascent fungal infections will cause increasing attrition of biodiversity, with wider implications for human and ecosystem health, unless steps are taken to tighten biosecurity worldwide. 相似文献