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Wan J Yourshaw M Mamsa H Rudnik-Schöneborn S Menezes MP Hong JE Leong DW Senderek J Salman MS Chitayat D Seeman P von Moers A Graul-Neumann L Kornberg AJ Castro-Gago M Sobrido MJ Sanefuji M Shieh PB Salamon N Kim RC Vinters HV Chen Z Zerres K Ryan MM Nelson SF Jen JC 《Nature genetics》2012,44(6):704-708
RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment, resulting in small brain size and poor motility, reminiscent of human clinical features, and these defects were largely rescued by co-injection with wild-type but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome core component gene that is responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration. 相似文献
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Varon R Gooding R Steglich C Marns L Tang H Angelicheva D Yong KK Ambrugger P Reinhold A Morar B Baas F Kwa M Tournev I Guerguelcheva V Kremensky I Lochmüller H Müllner-Eidenböck A Merlini L Neumann L Bürger J Walter M Swoboda K Thomas PK von Moers A Risch N Kalaydjieva L 《Nature genetics》2003,35(2):185-189
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The Hill equation and the origin of quantitative pharmacology 总被引:1,自引:0,他引:1
Rudolf Gesztelyi Judit Zsuga Adam Kemeny-Beke Balazs Varga Bela Juhasz Arpad Tosaki 《Archive for History of Exact Sciences》2012,66(4):427-438
This review addresses the 100-year-old Hill equation (published in January 22, 1910), the first formula relating the result
of a reversible association (e.g., concentration of a complex, magnitude of an effect) to the variable concentration of one
of the associating substances (the other being present in a constant and relatively low concentration). In addition, the Hill
equation was the first (and is the simplest) quantitative receptor model in pharmacology. Although the Hill equation is an
empirical receptor model (its parameters have only physico-chemical meaning for a simple ligand binding reaction), it requires
only minor a priori knowledge about the mechanism of action for the investigated agonist to reliably fit concentration-response
curve data and to yield useful results (in contrast to most of the advanced receptor models). Thus, the Hill equation has
remained an important tool for physiological and pharmacological investigations including drug discovery, moreover it serves
as a theoretical basis for the development of new pharmacological models. 相似文献
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