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71.
TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis 总被引:2,自引:0,他引:2
Kabashi E Valdmanis PN Dion P Spiegelman D McConkey BJ Vande Velde C Bouchard JP Lacomblez L Pochigaeva K Salachas F Pradat PF Camu W Meininger V Dupre N Rouleau GA 《Nature genetics》2008,40(5):572-574
Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis. 相似文献
72.
Park CC Ahn S Bloom JS Lin A Wang RT Wu T Sekar A Khan AH Farr CJ Lusis AJ Leahy RM Lange K Smith DJ 《Nature genetics》2008,40(4):421-429
We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The -2log10P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with -log10P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome. 相似文献
73.
Ross MT Grafham DV Coffey AJ Scherer S McLay K Muzny D Platzer M Howell GR Burrows C Bird CP Frankish A Lovell FL Howe KL Ashurst JL Fulton RS Sudbrak R Wen G Jones MC Hurles ME Andrews TD Scott CE Searle S Ramser J Whittaker A Deadman R Carter NP Hunt SE Chen R Cree A Gunaratne P Havlak P Hodgson A Metzker ML Richards S Scott G Steffen D Sodergren E Wheeler DA Worley KC Ainscough R Ambrose KD Ansari-Lari MA Aradhya S Ashwell RI Babbage AK Bagguley CL Ballabio A Banerjee R Barker GE Barlow KF 《Nature》2005,434(7031):325-337
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. 相似文献
74.
Sweet-Cordero A Mukherjee S Subramanian A You H Roix JJ Ladd-Acosta C Mesirov J Golub TR Jacks T 《Nature genetics》2005,37(1):48-55
Using advanced gene targeting methods, generating mouse models of cancer that accurately reproduce the genetic alterations present in human tumors is now relatively straightforward. The challenge is to determine to what extent such models faithfully mimic human disease with respect to the underlying molecular mechanisms that accompany tumor progression. Here we describe a method for comparing mouse models of cancer with human tumors using gene-expression profiling. We applied this method to the analysis of a model of Kras2-mediated lung cancer and found a good relationship to human lung adenocarcinoma, thereby validating the model. Furthermore, we found that whereas a gene-expression signature of KRAS2 activation was not identifiable when analyzing human tumors with known KRAS2 mutation status alone, integrating mouse and human data uncovered a gene-expression signature of KRAS2 mutation in human lung cancer. We confirmed the importance of this signature by gene-expression analysis of short hairpin RNA-mediated inhibition of oncogenic Kras2. These experiments identified both a pattern of gene expression indicative of KRAS2 mutation and potential effectors of oncogenic KRAS2 activity in human cancer. This approach provides a strategy for using genomic analysis of animal models to probe human disease. 相似文献
75.
Effects of 6-hydroxydopamine on sleep in the rat 总被引:1,自引:0,他引:1
76.
Walter Salvator Contro Johannes Viktor Feitzinger Rolf Hartmann Friedrich W. Ihloff Hans-Georg Märtl Friedemann Rex Matthias Schramm Horst Zehe 《Archive for History of Exact Sciences》1970,6(5):360-371
Zusammenfassung
Copernicus versucht, die Ptolemäischen Konstruktionen auf konzentrische Kreise und Epizykel zu reduzieren und aus ihnen ein wirklich einheitliches System zu schaffen. Bei der Umordnung, die er dazu vornimmt, bemüht er sich aber, so viel wie möglich vom Ptolemäischen System zu erhalten. Das punctum aequans ersetzt er bei den äußeren Planeten durch eine Näherungskonstruktion mit Hilfe eines Epizykels. Im Fall des Ptolemäischen Deferenten der Venus, der nach seinen Vorstellungen die Erdbahn wiedergibt, muß er einen dem punctum aequans annähernd gleichwertigen Epizykelmechanismus auf die Venusbahn verpflanzen.
Vorgelegt von
B. L. van der Waerden 相似文献
77.
78.
79.
L. Schenkel-Hulliger W. P. Koella A. Hartmann L. Maître 《Cellular and molecular life sciences : CMLS》1974,30(10):1168-1170
Zusammenfassung Thyrotropin-Releasing Hormon (TRH) erzeugt unmittelbar nach i.v. Injektion an Pentobarbital-narkotisierten Ratten einen feinschlägigen Tremor und Haarsträuben. Diese Symptome werden durch eine direkte zentralnervöse Wirkung von TRH und nicht durch Stimulation der Schilddrüse ausgelöst. Die Wirkung ist dosisabhängig und spezifisch für das Tripeptid pGlu-His-Pro.
Acknowledgments. The authors gratefully acknowledge the advice of Dr.P. A. Desaulles and Dr.W. Rittel and the skilled technical assistance of Mr.B. Latscha and Mr.J. C. Dalmer. 相似文献
Acknowledgments. The authors gratefully acknowledge the advice of Dr.P. A. Desaulles and Dr.W. Rittel and the skilled technical assistance of Mr.B. Latscha and Mr.J. C. Dalmer. 相似文献
80.
J. Gillman Christine Gilbert Isobel Spence 《Cellular and molecular life sciences : CMLS》1955,11(4):157-158
Zusammenfassung Die Entstehung von Reticulosarkom bei Ratten nach mehrmaliger Injektion von Trypanblau kann unterdrückt werden durch Entkräftung, Verabreichung anti-thyreoidaler Mittel und durch alle andern Faktoren, welche den Stoffwechsel herabsetzen. 相似文献