排序方式: 共有74条查询结果,搜索用时 15 毫秒
41.
Janecke AR Thompson DA Utermann G Becker C Hübner CA Schmid E McHenry CL Nair AR Rüschendorf F Heckenlively J Wissinger B Nürnberg P Gal A 《Nature genetics》2004,36(8):850-854
We identified three consanguineous Austrian kindreds with 15 members affected by autosomal recessive childhood-onset severe retinal dystrophy, a genetically heterogeneous group of disorders characterized by degeneration of the photoreceptor cells. A whole-genome scan by microarray analysis of single-nucleotide polymorphisms (ref. 2) identified a founder haplotype and defined a critical interval of 1.53 cM on chromosome 14q23.3-q24.1 that contains the gene associated with this form of retinal dystrophy. RDH12 maps in this region and encodes a retinol dehydrogenase proposed to function in the visual cycle. A homozygous 677A-->G transition (resulting in Y226C) in RDH12 was present in all affected family members studied, as well as in two Austrian individuals with sporadic retinal dystrophy. We identified additional mutations in RDH12 in 3 of 89 non-Austrian individuals with retinal dystrophy: a 5-nucleotide deletion (806delCCCTG) and the transition 565C-->T (resulting in Q189X), each in the homozygous state, and 146C-->T (resulting in T49M) and 184C-->T (resulting in R62X) in compound heterozygosity. When expressed in COS-7 cells, Cys226 and Met49 variants had diminished and aberrant activity, respectively, in interconverting isomers of retinol and retinal. The severe visual impairment of individuals with mutations in RDH12 is in marked contrast to the mild visual deficiency in individuals with fundus albipunctatus caused by mutations in RDH5, encoding another retinal dehydrogenase. Our studies show that RDH12 is associated with retinal dystrophy and encodes an enzyme with a unique, nonredundant role in the photoreceptor cells. 相似文献
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Giridhar Pulletikurthi Bj?rn B?decker Andriy Borodin Bernd Weidenfeller Frank Endres 《自然科学进展(英文版)》2015,25(6):603-611
The addition of 1-butylpyrrolidine to AlCl_3 results in the formation of an electrolyte that is suited to Al deposition.The feasibility of electrodepositing Al from the synthesized electrolyte was investigated.Several compositions of AlCl_3 and 1-butylpyrrolidine were prepared for this purpose.These mixtures show a different phase behavior at various compositions of AlCl_3 and 1-butylpyrrolidine.IR,Raman and NMR spectroscopy were employed to characterize the synthesized liquids.Among the prepared compositions,1:1.2 mol ratio of 1-butylpyrrolidine:AlCl_3 and the upper phase of 1:1.3 mol ratio of 1-butylpyrrolidine:AlCl_3 were found to be suitable for Al electrodeposition at room temperature(RT).Uniform and thick( mm thick) layers of Al were obtained on copper at RT.Al deposition occured from the cationic species of AlCl_3 xLty(where x r 2,y ? 1–2,and L ? 1-butylpyrrolidine) in this electrolyte.This behavior is contrary to the well investigated classic AlCl_3 based ionic liquids,where the deposition of Al occurs mainly from anionic Al2 Cl 7ions. 相似文献
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Rock MJ Prenen J Funari VA Funari TL Merriman B Nelson SF Lachman RS Wilcox WR Reyno S Quadrelli R Vaglio A Owsianik G Janssens A Voets T Ikegawa S Nagai T Rimoin DL Nilius B Cohn DH 《Nature genetics》2008,40(8):999-1003
The brachyolmias constitute a clinically and genetically heterogeneous group of skeletal dysplasias characterized by a short trunk, scoliosis and mild short stature. Here, we identify a locus for an autosomal dominant form of brachyolmia on chromosome 12q24.1-12q24.2. Among the genes in the genetic interval, we selected TRPV4, which encodes a calcium permeable cation channel of the transient receptor potential (TRP) vanilloid family, as a candidate gene because of its cartilage-selective gene expression pattern. In two families with the phenotype, we identified point mutations in TRPV4 that encoded R616Q and V620I substitutions, respectively. Patch clamp studies of transfected HEK cells showed that both mutations resulted in a dramatic gain of function characterized by increased constitutive activity and elevated channel activation by either mechano-stimulation or agonist stimulation by arachidonic acid or the TRPV4-specific agonist 4alpha-phorbol 12,13-didecanoate (4alphaPDD). This study thus defines a previously unknown mechanism, activation of a calcium-permeable TRP ion channel, in skeletal dysplasia pathogenesis. 相似文献
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'Water-tastes' are gustatory after-impressions elicited by water following the removal of a chemical solution from the mouth, akin to colour after-images appearing on 'white' paper after fixation on coloured images. Unlike colour after-images, gustatory after-effects are poorly understood. One theory posits that 'water-tastes' are adaptation phenomena, in which adaptation to one taste solution causes the water presented subsequently to act as a taste stimulus. An alternative hypothesis is that removal of the stimulus upon rinsing generates a receptor-based, positive, off-response in taste-receptor cells, ultimately inducing a gustatory perception. Here we show that a sweet 'water-taste' is elicited when sweet-taste inhibitors are rinsed away. Responses of cultured cells expressing the human sweetener receptor directly parallel the psychophysical responses-water rinses remove the inhibitor from the heteromeric sweetener receptor TAS1R2-TAS1R3, which activates cells and results in the perception of strong sweetness from pure water. This 'rebound' activity occurs when equilibrium forces on the two-state allosteric sweet receptors result in their coordinated shift to the activated state upon being released from inhibition by rinsing. 相似文献
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Initial applications of prediction markets (PMs) indicate that they provide good forecasting instruments in many settings, such as elections, the box office, or product sales. One particular characteristic of these ‘first‐generation’ (G1) PMs is that they link the payoff value of a stock's share to the outcome of an event. Recently, ‘second‐generation’ (G2) PMs have introduced alternative mechanisms to determine payoff values which allow them to be used as preference markets for determining preferences for product concepts or as idea markets for generating and evaluating new product ideas. Three different G2 payoff mechanisms appear in the existing literature, but they have never been compared. This study conceptually and empirically compares the forecasting accuracy of the three G2 payoff mechanisms and investigates their influence on participants' trading behavior. We find that G2 payoff mechanisms perform almost as well as their G1 counterpart, and trading behavior is very similar in both markets (i.e. trading prices and trading volume), except during the very last trading hours of the market. These results indicate that G2 PMs are valid instruments and support their applicability shown in previous studies for developing new product ideas or evaluating new product concepts. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
48.
Roell W Lewalter T Sasse P Tallini YN Choi BR Breitbach M Doran R Becher UM Hwang SM Bostani T von Maltzahn J Hofmann A Reining S Eiberger B Gabris B Pfeifer A Welz A Willecke K Salama G Schrickel JW Kotlikoff MI Fleischmann BK 《Nature》2007,450(7171):819-824
Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy. 相似文献
49.
Bernd Fritzsch Daniel F. Eberl Kirk W. Beisel 《Cellular and molecular life sciences : CMLS》2010,67(18):3089-3099
In mouse ear development, two bHLH genes, Atoh1 and Neurog1, are essential for hair cell and sensory neuron differentiation. Evolution converted the original simple atonal-dependent neurosensory cell formation program of diploblasts into the derived developmental program of vertebrates that generates
two neurosensory cell types, the sensory neuron and the sensory hair cell. This transformation was achieved through gene multiplication
in ancestral triploblasts resulting in the expansion of the atonal
bHLH gene family. Novel genes of the Neurogenin and NeuroD families are upregulated prior to the expression of Atoh1. Recent data suggest that NeuroD and Neurogenin were lost or their function in neuronal specification reduced in flies, thus changing our perception of the evolution of
these genes. This sequence of expression changes was accompanied by modification of the E-box binding sites of these genes
to regulate different downstream genes and to form inhibitory loops among each other, thus fine-tuning expression transitions. 相似文献
50.
Mutations in SEPT9 cause hereditary neuralgic amyotrophy 总被引:7,自引:0,他引:7
Kuhlenbäumer G Hannibal MC Nelis E Schirmacher A Verpoorten N Meuleman J Watts GD De Vriendt E Young P Stögbauer F Halfter H Irobi J Goossens D Del-Favero J Betz BG Hor H Kurlemann G Bird TD Airaksinen E Mononen T Serradell AP Prats JM Van Broeckhoven C De Jonghe P Timmerman V Ringelstein EB Chance PF 《Nature genetics》2005,37(10):1044-1046
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis. 相似文献