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Voineagu I Wang X Johnston P Lowe JK Tian Y Horvath S Mill J Cantor RM Blencowe BJ Geschwind DH 《Nature》2011,474(7351):380-384
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Horvath A Boikos S Giatzakis C Robinson-White A Groussin L Griffin KJ Stein E Levine E Delimpasi G Hsiao HP Keil M Heyerdahl S Matyakhina L Libè R Fratticci A Kirschner LS Cramer K Gaillard RC Bertagna X Carney JA Bertherat J Bossis I Stratakis CA 《Nature genetics》2006,38(7):794-800
Phosphodiesterases (PDEs) regulate cyclic nucleotide levels. Increased cyclic AMP (cAMP) signaling has been associated with PRKAR1A or GNAS mutations and leads to adrenocortical tumors and Cushing syndrome. We investigated the genetic source of Cushing syndrome in individuals with adrenocortical hyperplasia that was not caused by known defects. We performed genome-wide SNP genotyping, including the adrenocortical tumor DNA. The region with the highest probability to harbor a susceptibility gene by loss of heterozygosity (LOH) and other analyses was 2q31-2q35. We identified mutations disrupting the expression of the PDE11A isoform-4 gene (PDE11A) in three kindreds. Tumor tissues showed 2q31-2q35 LOH, decreased protein expression and high cyclic nucleotide levels and cAMP-responsive element binding protein (CREB) phosphorylation. PDE11A codes for a dual-specificity PDE that is expressed in adrenal cortex and is partially inhibited by tadalafil and other PDE inhibitors; its germline inactivation is associated with adrenocortical hyperplasia, suggesting another means by which dysregulation of cAMP signaling causes endocrine tumors. 相似文献
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Becker-Heck A Zohn IE Okabe N Pollock A Lenhart KB Sullivan-Brown J McSheene J Loges NT Olbrich H Haeffner K Fliegauf M Horvath J Reinhardt R Nielsen KG Marthin JK Baktai G Anderson KV Geisler R Niswander L Omran H Burdine RD 《Nature genetics》2011,43(1):79-84
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD. 相似文献
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The Medves Area lies close to the Hungarian-Slovak boundary in North Hungary. Having "horst-graben-type" geological structure it can be characterised by steeply emerging horst-like hills and between them narrow trenches and deeply dissected erosional valleys. The recent morphology of the Medves Area is determined by four main elements: the structure, the petrographic setting, the exo-genic processes and the anthropogenic effects. In spite of the domination of the Oligocene-Miocene sedimentary rocks great part of the area is covered by Pliocene basalts having either stratovolcanic structure or consisting of only lavas, forming lavaplateaus, small cones, dykes or necks. In spite of the strong denudation their original form dominates yet. The decrease of the sheet of the Medves Plateau was considerable only on the rims by parallel retreat. In the southern part of the Medves Area the evolution of the landscape was determined mainly by exogenic processes. The great density of the valleys is very significant, but it is interesting that many tributary valleys are dry valleys, which can be explained by neotectonic movements and young captures. Anthropogenic forms are very frequent in the Medves Area, where the change of the natural environment caused by human activity is above average. Especially the landscape forming effects of the mining of basalt and browncoal and that of the related industry and infrastructure changed the surface. Very interesting are the depressions on the surface caused by collapse of underground galleries, moreover sometimes trench-like deep fissures came into being. 相似文献
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Summary Fine structural studies of various endocrine adenomas indicate that mitochondria may serve as progenitors of centrioles and cilia.Acknowledgments. This work was supported in part by a grant from the Ontario Cancer Treatment and Research Foundation. The excellent technical assistance of Mrs.Gezina Ilse and the secreterial help of Mrs.Wanda Mikitson are gratefully acknowledged. 相似文献
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The acids accumulating in soils and controlling the solution of carbonates including the predominant CO2, mostly derive from three processes: i) root respiration of higher plants; ii) decomposition of soil organic matter by microorganisms (microbiota) and iii) other decomposition processes not associated with microbial activities. The solution effect under rendzina soils is primarily used for the dissolution of the enclosed limestone fragments and thus here the solution of bedrock is of limited scale. Below karst soils of high clay content the corrosion of bedrock is more intensive than under rendzinas. On the whole, the amount of carbonates dissolved and transported into the depths of the karst is smaller than below rendzinas. In each soil type studied the solution caused by microbial activities manifold exceeds the rate of solution resulting from temperature factor but there is a manifest dropping trend from rendzina to clays. 相似文献
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Changing the identity of a transfer RNA 总被引:36,自引:0,他引:36
A leucine transfer RNA has been transformed into a serine transfer RNA by changing 12 nucleotides. This result indicates that a limited set of residues determine tRNA identity. 相似文献
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D. J. McComb N. Ryan E. Horvath K. Kovacs I. Domokos F. A. Laszlo 《Cellular and molecular life sciences : CMLS》1979,35(10):1409-1410
Summary Following 2 weeks of administration of 2-bromo--ergocryptine, a marked decrease was observed in prolactin immunoreactivity of the grafted pituitaries, whereas no reduction was noted in the intrasellar pituitaries. No evidence of crinophagy was revealed by electron microscopy in prolactin cells of 2-bromo--ergocryptine-treated rats.Acknowledgments. This work was supported in part by the Medical Research Council of Canada (grant MA-6349). The excellent technical assistance of Mrs Cynthia Edwards and secretarial help of Mrs Wanda Wlodarski are gratefully acknowledged. 相似文献