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161.
Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
162.
Risheg H Graham JM Clark RD Rogers RC Opitz JM Moeschler JB Peiffer AP May M Joseph SM Jones JR Stevenson RE Schwartz CE Friez MJ 《Nature genetics》2007,39(4):451-453
Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex. 相似文献
163.
164.
Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies 总被引:3,自引:0,他引:3
Borrell-Pagès M Zala D Humbert S Saudou F 《Cellular and molecular life sciences : CMLS》2006,63(22):2642-2660
Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary
movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains
a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin.
Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational
modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the
brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood
but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses
on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to
new therapeutic approaches.
Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006 相似文献
165.
Human β-defensins 总被引:1,自引:0,他引:1
Pazgier M Hoover DM Yang D Lu W Lubkowski J 《Cellular and molecular life sciences : CMLS》2006,63(11):1294-1313
166.
Increasing evidence implies altered signaling through the neurotrophic receptor tyrosine kinase TrkB in promoting tumor formation
and metastasis. TrkB, sometimes in conjunction with its primary ligand BDNF, is often overexpressed in a variety of human
cancers, ranging from neuroblastomas to pancreatic ductal adenocarcinomas, in which it may allow tumor expansion and contribute
to resistance to anti-tumor agents. In vitro, TrkB acts as a potent suppressor of anoikis (detachment-induced apoptosis), which is associated with the acquisition of
an aggressive tumorigenic and metastatic phenotype in vivo. In view of its predicted contribution to tumorigenicity and metastasis in humans, TrkB corresponds to a potential drug target,
and preclinical models have already been established. The encouraging results of pharmacological Trk inhibitors in tumor xenograft
models suggest that TrkB inhibition may represent a promising novel anti-tumor therapeutic strategy. This hypothesis is currently
being evaluated in clinical trials. Here, we will discuss the latest developments on TrkB in these contexts as well as highlight
some critical questions that remain to be addressed for evaluating TrkB as a therapeutic target in cancer.
Received 12 October 2005; received after revision 19 December 2005; accepted 11 January 2006 相似文献
167.
传统的正向遗传学主要用于克隆表型或功能已确定的基因。转座子标签突变体可用随机标签法从带有活性转座子的自交后代中筛选得到,或用定向标签法从杂交一代中筛选得到,即用目的基因的隐性突变统合体与具高度活性转座号的统合体杂交,极大多数的FI个体为正常表型,但其中会有极少量的表现隐性性状的转庄子插入突变体。正向基因标签和克隆法在利用异源和低拷贝数品系时尤其有用。采用反向fCR或热不对称交替PCR(TAIL-PCR)且很容易从单拷贝或低拷贝数品系中获得插入于两侧的基因组序列。TAIL-PCR由三轮连续的半巢式PCR组成,所… 相似文献
168.
Structural,morphological, and optical properties of tin(Ⅳ) oxide nanoparticles synthesized using Camellia sinensis extract: a green approach
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Tin oxide (SnO2) nanoparticles were cost-effectively synthesized using nontoxic chemicals and green tea (Camellia sinensis) extract via a green synthesis method.The structural properties of the obtained nanoparticles were studied using X-ray diffraction,which indicated that the crystallite size was less than 20 nm.The particle size and morphology of the nanoparticles were analyzed using scanning electron microscopy and transmission electron microscopy.The morphological analysis revealed agglomerated spherical nanoparticles with sizes varying from 5 to 30 nm.The optical properties of the nanoparticles' band gap were characterized using diffuse reflectance spectroscopy.The band gap was found to decrease with increasing annealing temperature.The O vacancy defects were analyzed using photoluminescence spectroscopy.The increase in the crystallite size,decreasing band gap,and the increasing intensities of the UV and visible emission peaks indicated that the green-synthesized SnO2 may play future important roles in catalysis and optoelectronic devices. 相似文献
169.
The aim of this study was to determine the structural, compositional, and mineralogical composition of carbonatitic copper sulfide concentrator plant streams. Three samples, each from a different stream(run of mine(ROM), concentrate, and tailings) of a copper concentrator were characterized using various techniques, including stereomicroscopy, X-ray fluorescence, X-ray diffraction, Fourier transform infrared(FTIR) spectroscopy, scanning electron microscopy(SEM) in conjunction with energy-dispersive X-ray spectroscopy(EDS), and optical microscopy. The results reveal that each stream possesses its own unique compositional features. Carbonate minerals associated with calcite and dolomite, followed by quartz, remain the major minerals in both the ROM and tails streams. In the ROM stream, chalcopyrite appears to occur as veins within the carbonatite-hosting ore body. Mineral phase mutation was discovered in the tails stream because magnetite formerly identified in the ROM as the primary iron oxide had evolved into hematite. This metamorphosis was likely promoted by the concentration process. The concentration process was effective, upgrading the chalcopyrite content from 2 wt% in the ROM stream to 58 wt% in the concentrate stream; it was accompanied by bornite(4 wt%), anilite(3 wt%), and digenite(2.5 wt%). In addition, the concentrate stream exhibited properties distinctive from those of the other streams. The FTIR analysis showed the existence of a sulfide group related to the chalcopyrite mineral. Free chalcopyrite grains were observed in the concentrate by SEM analysis, and their mineral presence was supported by the EDS analysis results. All characterization techniques corresponded well with each other regarding the structure, chemistry, and composition of the samples. 相似文献
170.
Luiz A. Rocha Joseph D. DiBattista Tane H. Sinclair-Taylor Michael L. Berumen 《Journal of Natural History》2020,54(15-16):1019-1023
ABSTRACT Here we document three cases of mimicry in coral reef fishes not previously reported in the literature involving two groupers (Epinephelus leucogrammicus and Plectropomus marisrubri) and a soapfish (Diploprion drachi) as mimics, and two wrasses (Larabicus quadrilineatus and Cheilinus quinquecinctus) and a blenny (Meiacanthus nigrolineatus) as models. All three cases are of aggressive mimicry, with a predatory species mimicking a harmless one, and in one of the cases, the mimicry is also Müllerian, where both the predator and harmless species are unpalatable. 相似文献