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A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis 总被引:14,自引:0,他引:14
Cooper MK Wassif CA Krakowiak PA Taipale J Gong R Kelley RI Porter FD Beachy PA 《Nature genetics》2003,33(4):508-513
Smith-Lemli-Opitz syndrome (SLOS), desmosterolosis and lathosterolosis are human syndromes caused by defects in the final stages of cholesterol biosynthesis. Many of the developmental malformations in these syndromes occur in tissues and structures whose embryonic patterning depends on signaling by the Hedgehog (Hh) family of secreted proteins. Here we report that response to the Hh signal is compromised in mutant cells from mouse models of SLOS and lathosterolosis and in normal cells pharmacologically depleted of sterols. We show that decreasing levels of cellular sterols correlate with diminishing responsiveness to the Hh signal. This diminished response occurs at sterol levels sufficient for normal autoprocessing of Hh protein, which requires cholesterol as cofactor and covalent adduct. We further find that sterol depletion affects the activity of Smoothened (Smo), an essential component of the Hh signal transduction apparatus. 相似文献
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Theodore M. Porter 《Annals of science》2013,70(5):543-570
This paper explores the origins of the analytical definition of simple substance, a concept whose central importance in the new chemistry of Lavoisier and his colleagues is now widely recognized. I argue that this notion derived from the practical activities of metallurgists and mineral assayers, and that the theoretical elaboration necessary for the analytical concept to be understood as relevant to chemistry was inspired by the efforts of enlightened rulers in Sweden and Germany to turn chemical science to the benefit of mining—and thus of the various state treasuries. The involvement of chemically-literate mineralogists in the mining industry led them to adopt the principle that analytically-determined composition was a far more essential aspect of minerals than any mere congeries of properties. The same men who pioneered the analytical notion of simple substance also inaugurated the attempt to define a nomenclature for chemistry based exclusively on composition, as determined in the laboratory. 相似文献
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This report includes data collected during an investigation by Brigham Young University personnel from 1971 to 1976, as well as a literature review. The fauna of the Kaiparowits Basin is represented by 7 species of amphibians (1 salamander, 5 toads, and 1 tree frog), 29 species of reptiles (1 turtle, 16 lizards, and 12 snakes), 183 species of birds (plus 2 hypothetical), and 74 species of mammals. Geographic distribution of the various species within the basin are discussed. Birds are categorized according to their population and seasonal status. Avian habitat relationships are discussed, and extensions of range are reported for 5 species of birds. Three threatened or endangered avian species occur in the basin. Four avian species seem to have declined significantly in numbers in recent years. 相似文献
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Complete nucleotide sequence of an influenza virus haemagglutinin gene from cloned DNA 总被引:69,自引:0,他引:69
A synthetic fowl plague virus (FPV) haemagglutinin gene has been cloned in bacteria and the complete sequence of the RNA gene deduced. It is 1,742 nucleotides long and the mRNA codes for 56.3 amino acids in an uninterrupted sequence. The nature of some of the important domains in the haemagglutinin has been established, and their structure is discussed in relation to their function. Extensive amino acid sequence homologies exist between FPV and human influenza haemagglutinins. 相似文献