排序方式: 共有24条查询结果,搜索用时 46 毫秒
1.
Rui M Costa Nikolai B Federov Jeff H Kogan Geoffrey G Murphy Joel Stern Masuo Ohno Raju Kucherlapati Tyler Jacks Alcino J Silva 《Nature》2002,415(6871):526-530
Neurofibromatosis type I (NF1) is one of the most common single-gene disorders that causes learning deficits in humans. Mice carrying a heterozygous null mutation of the Nfl gene (Nfl(+/-) show important features of the learning deficits associated with NF1 (ref. 2). Although neurofibromin has several known properties and functions, including Ras GTPase-activating protein activity, adenylyl cyclase modulation and microtubule binding, it is unclear which of these are essential for learning in mice and humans. Here we show that the learning deficits of Nf1(+/-) mice can be rescued by genetic and pharmacological manipulations that decrease Ras function. We also show that the Nf1(+/-) mice have increased GABA (gamma-amino butyric acid)-mediated inhibition and specific deficits in long-term potentiation, both of which can be reversed by decreasing Ras function. Our results indicate that the learning deficits associated with NF1 may be caused by excessive Ras activity, which leads to impairments in long-term potentiation caused by increased GABA-mediated inhibition. Our findings have implications for the development of treatments for learning deficits associated with NF1. 相似文献
2.
Anderson BH Kasher PR Mayer J Szynkiewicz M Jenkinson EM Bhaskar SS Urquhart JE Daly SB Dickerson JE O'Sullivan J Leibundgut EO Muter J Abdel-Salem GM Babul-Hirji R Baxter P Berger A Bonafé L Brunstom-Hernandez JE Buckard JA Chitayat D Chong WK Cordelli DM Ferreira P Fluss J Forrest EH Franzoni E Garone C Hammans SR Houge G Hughes I Jacquemont S Jeannet PY Jefferson RJ Kumar R Kutschke G Lundberg S Lourenço CM Mehta R Naidu S Nischal KK Nunes L Ounap K Philippart M Prabhakar P Risen SR 《Nature genetics》2012,44(3):338-342
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity. 相似文献
3.
Roberts AE Araki T Swanson KD Montgomery KT Schiripo TA Joshi VA Li L Yassin Y Tamburino AM Neel BG Kucherlapati RS 《Nature genetics》2007,39(1):70-74
Noonan syndrome, the most common single-gene cause of congenital heart disease, is characterized by short stature, characteristic facies, learning problems and leukemia predisposition. Gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases. SHP2 is required for RAS-ERK MAP kinase (MAPK) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. KRAS mutations account for <5% of cases of Noonan syndrome, but the gene(s) responsible for the remainder are unknown. We identified missense mutations in SOS1, which encodes an essential RAS guanine nucleotide-exchange factor (RAS-GEF), in approximately 20% of cases of Noonan syndrome without PTPN11 mutation. The prevalence of specific cardiac defects differs in SOS1 mutation-associated Noonan syndrome. Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. Our results identify SOS1 mutants as a major cause of Noonan syndrome, representing the first example of activating GEF mutations associated with human disease and providing new insights into RAS-GEF regulation. 相似文献
4.
S. Mastanaiah D. Chengal Raju K. S. Swami 《Cellular and molecular life sciences : CMLS》1977,33(8):1051-1052
Summary The activity of isocitrate dehydrogenase was assayed in the pedipalpal muscle and hepatopancreas of scorption, Heterometrus fulvipes. The enzyme activity showed a circadian rhythmicity with a peak value at 20.00 h in both the tissues. 相似文献
5.
R. V. Krishnamoorthy D. Chengal Raju V. Chandrasekharam 《Cellular and molecular life sciences : CMLS》1971,27(12):1408-1409
Zusammenfassung Es wird gezeigt, dass die erhöhte autolytische Abbaugeschwindigkeit im denervierten Muskel von Bedeutung für den Proteinumsatz ist und immer noch das zentrale Problem der Veränderungen darstellt, die bei Denervierung — hier Durchschneidung des Ischiadicus — auftreten. 相似文献
6.
Danda Srinivas Rao Tadiparthi Venkata VijayaKumar Sripada Subba Rao Swarna Prabhakar Guntamadugu Bhaskar Raju 《矿物冶金与材料学报》2011,18(5):515-522
The recovery of iron from the screw classifier overflow slimes by direct flotation was studied. The relative effectiveness of sodium silicates with different silica-to-soda mole ratios as depressants for silica and silicate bearing minerals was investigated. Silica-to-soda mole ratio and silicate dosage were found to have significant effect on the separation efficiency. The results show that an increase of Fe content in the concentrate is observed with concomitant reduction in SiO2 and Al2O3 levels when a particular type of sodium silicate at a proper dosage is used. The concentrate of 58.89wt% Fe, 4.68wt% SiO2, and 5.28wt% Al2O3 with the weight recovery of 38.74% and the metal recovery of 41.13% can be obtained from the iron ore slimes with 54.44wt% Fe, 6.72wt% SiO2, and 6.80wt% Al2O3, when Na2SiO3 with a silica-to-soda mole ratio of 2.19 is used as a depressant at a feed rate of 0.2 kg/t. 相似文献
7.
8.
Wang Y Putnam CD Kane MF Zhang W Edelmann L Russell R Carrión DV Chin L Kucherlapati R Kolodner RD Edelmann W 《Nature genetics》2005,37(7):750-755
Most cancers have multiple chromosomal rearrangements; the molecular mechanisms that generate them remain largely unknown. Mice carrying a heterozygous missense change in one of the DNA-binding domains of Rpa1 develop lymphoid tumors, and their homozygous littermates succumb to early embryonic lethality. Array comparative genomic hybridization of the tumors identified large-scale chromosomal changes as well as segmental gains and losses. The Rpa1 mutation resulted in defects in DNA double-strand break repair and precipitated chromosomal breaks as well as aneuploidy in primary heterozygous mutant mouse embryonic fibroblasts. The equivalent mutation in yeast is hypomorphic and semidominant and enhanced the formation of gross chromosomal rearrangements in multiple genetic backgrounds. These results indicate that Rpa1 functions in DNA metabolism are essential for the maintenance of chromosomal stability and tumor suppression. 相似文献
9.
S. Mastanaiah D. Chengal Raju D. Ravi Varma K. S. Swami 《Cellular and molecular life sciences : CMLS》1979,35(1):69-70
Summary The activity levels of aldolase and isocitrate dehydrogenase were assayed in the heart muscle of scorpion,Heterometrus fulvipes. The enzyme activities showed a circadian rhythmicity with a peak value at 20.00 h in the heart muscle. 相似文献
10.
Zusammenfassung Herz und Magenmuskulatur des Frosches verlieren in halb-isotoner Rohrzuckerlösung innert 1 h alles Natrium. Trotzdem bleibt die spontane Kontraktilität erhalten. Natrium ist also für die Erregbarkeit dieser Muskeln nicht Voraussetzung. 相似文献