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121.
Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish 总被引:29,自引:0,他引:29
J R Kelsoe E I Ginns J A Egeland D S Gerhard A M Goldstein S J Bale D L Pauls R T Long K K Kidd G Conte 《Nature》1989,342(6247):238-243
Reanalysis of an Old Order Amish pedigree, to include several new individuals and two changes in clinical status, markedly reduces the probability of linkage between bipolar affective disorder and the Harvey-ras-1 oncogene and insulin loci on chromosome 11. This linkage can be excluded using a large lateral extension of the original Amish pedigree. 相似文献
122.
Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. 总被引:24,自引:0,他引:24
Proteolytic processing of amyloid precursor protein (APP) generates amyloid-beta peptide and has been implicated in the pathogenesis of Alzheimer's disease. However, the normal function of APP, whether this function is related to the proteolytic processing of APP, and where this processing takes place in neurons in vivo remain unknown. We have previously shown that the axonal transport of APP in neurons is mediated by the direct binding of APP to the kinesin light chain subunit of kinesin-I, a microtubule motor protein. Here we identify an axonal membrane compartment that contains APP, beta-secretase and presenilin-1. The fast anterograde axonal transport of this compartment is mediated by APP and kinesin-I. Proteolytic processing of APP can occur in the compartment in vitro and in vivo in axons. This proteolysis generates amyloid-beta and a carboxy-terminal fragment of APP, and liberates kinesin-I from the membrane. These results suggest that APP functions as a kinesin-I membrane receptor, mediating the axonal transport of beta-secretase and presenilin-1, and that processing of APP to amyloid-beta by secretases can occur in an axonal membrane compartment transported by kinesin-I. 相似文献
123.
Zody MC Garber M Adams DJ Sharpe T Harrow J Lupski JR Nicholson C Searle SM Wilming L Young SK Abouelleil A Allen NR Bi W Bloom T Borowsky ML Bugalter BE Butler J Chang JL Chen CK Cook A Corum B Cuomo CA de Jong PJ DeCaprio D Dewar K FitzGerald M Gilbert J Gibson R Gnerre S Goldstein S Grafham DV Grocock R Hafez N Hagopian DS Hart E Norman CH Humphray S Jaffe DB Jones M Kamal M Khodiyar VK LaButti K Laird G Lehoczky J Liu X Lokyitsang T Loveland J Lui A Macdonald P Major JE Matthews L Mauceli E 《Nature》2006,440(7087):1045-1049
Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome. 相似文献
124.
Zusammenfassung Phenylethylamin, 3-Methoxy-dopamin undp-Hydroxyamphetamin werden durch Dopamin--oxidase in die entsprechende-Hydroxy-Verbindung umgewandelt.
This work was supported by grants from the National Institutes of Health. 相似文献
This work was supported by grants from the National Institutes of Health. 相似文献
125.
M. Goldstein A. J. Friedhoff C. Simmons N. N. Prochoroff 《Cellular and molecular life sciences : CMLS》1959,15(7):254-256
Zusammenfassung Homogenate aus Gehirn wurden mit 3-Hydroxytyramine-1-C14 inkubiert. Als Stoffwechselprodukt wurde aus der sauren Fraktion radioaktive 3,4-Dioxyphenylessigsäure isoliert. Aus der basischen Fraktion wurden drei radioaktive Zonen papierchromatographisch isoliert. Die erste Zone konnte noch nicht identifiziert werden. Die zweite wurde als 3-Hydroxytyramin und die dritte als 3-Methoxytyramin erkannt. Die mögliche Rolle der Stoffwechselprodukte von 3-Hydroxytyramin beim Parkinson-Syndrom wird diskutiert.
This study was supported in part by United States Public Health Service Grant M 2717.The authors are grateful toR. J. Floody, M. D. of Hoffmann-La Roche Inc., for providing us with iproniazid. 相似文献
This study was supported in part by United States Public Health Service Grant M 2717.The authors are grateful toR. J. Floody, M. D. of Hoffmann-La Roche Inc., for providing us with iproniazid. 相似文献
126.
Zusammenfassung Die enzymatische Bildung des Norepinephrins und des Epinephrins wurde als Funktion des pH und der Zusammensetzung der Puffergemische untersucht. Eine maximale enzymatische Aktivität wurde bei einem pH von 5,5 beobachtet. Durch Zusatz von Phosphatpuffer wird die Aktivität gehemmt. Eine maximale Hemmung der enzymatischen Norepinephrinbildung durch DPA und Tryptamin wurde bei einem pH von 5,5 und durch Adrenalon bei einem pH von 6,5 festgestellt. Der Reaktionsmechanismus wurde auf Grund der Ergebnisse erläutert. 相似文献
127.
128.
The Earth's radiation belts--also known as the Van Allen belts--contain high-energy electrons trapped on magnetic field lines. The centre of the outer belt is usually 20,000-25,000 km from Earth. The region between the belts is normally devoid of particles, and is accordingly favoured as a location for spacecraft operation because of the benign environment. Here we report that the outer Van Allen belt was compressed dramatically by a solar storm known as the 'Hallowe'en storm' of 2003. From 1 to 10 November, the outer belt had its centre only approximately 10,000 km from Earth's equatorial surface, and the plasmasphere was similarly displaced inwards. The region between the belts became the location of high particle radiation intensity. This remarkable deformation of the entire magnetosphere implies surprisingly powerful acceleration and loss processes deep within the magnetosphere. 相似文献
129.
In genetic control of disease, does 'race' matter? 总被引:3,自引:0,他引:3
130.
Yamada K Andrews C Chan WM McKeown CA Magli A de Berardinis T Loewenstein A Lazar M O'Keefe M Letson R London A Ruttum M Matsumoto N Saito N Morris L Del Monte M Johnson RH Uyama E Houtman WA de Vries B Carlow TJ Hart BL Krawiecki N Shoffner J Vogel MC Katowitz J Goldstein SM Levin AV Sener EC Ozturk BT Akarsu AN Brodsky MC Hanisch F Cruse RP Zubcov AA Robb RM Roggenkäemper P Gottlob I Kowal L Battu R Traboulsi EI Franceschini P Newlin A Demer JL Engle EC 《Nature genetics》2003,35(4):318-321
Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis. 相似文献