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排序方式: 共有185条查询结果,搜索用时 140 毫秒
81.
Shaheen Akhtar Julia Grizenkova Adam Wenborn Holger Hummerich Mar Fernandez de Marco Sebastian Brandner John Collinge Sarah E. Lloyd 《PloS one》2013,8(1)
Prion infections, causing neurodegenerative conditions such as Creutzfeldt-Jakob disease and kuru in humans, scrapie in sheep and BSE in cattle are characterised by prolonged and variable incubation periods that are faithfully reproduced in mouse models. Incubation time is partly determined by genetic factors including polymorphisms in the prion protein gene. Quantitative trait loci studies in mice and human genome-wide association studies have confirmed that multiple genes are involved. Candidate gene approaches have also been used and identified App, Il1-r1 and Sod1 as affecting incubation times. In this study we looked for an association between App, Il1-r1 and Sod1 representative SNPs and prion disease incubation time in the Northport heterogeneous stock of mice inoculated with the Chandler/RML prion strain. No association was seen with App, however, significant associations were seen with Il1-r1 (P = 0.02) and Sod1 (P<0.0001) suggesting that polymorphisms at these loci contribute to the natural variation observed in incubation time. Furthermore, following challenge with Chandler/RML, ME7 and MRC2 prion strains, Sod1 deficient mice showed highly significant reductions in incubation time of 20, 13 and 24%, respectively. No differences were detected in Sod1 expression or activity. Our data confirm the protective role of endogenous Sod1 in prion disease. 相似文献
82.
83.
A J Collinge 《The British journal of physiological optics》1979,33(2):21-28
An experiment is undertaken to investigate the relationship between "sighting" and motor dominance. A review of recent work on the neurophysiology of vision is carried out and an attempt to explain ocular dominance using this is made. 相似文献
84.
Hosszu LL Wells MA Jackson GS Jones S Batchelor M Clarke AR Craven CJ Waltho JP Collinge J 《Biochemistry》2005,44(50):16649-16657
The role of conformational intermediates in the conversion of prion protein from its normal cellular form (PrP(C)) to the disease-associated "scrapie" form (PrP(Sc)) remains unknown. To look for such intermediates in equilibrium conditions, we have examined the unfolding transitions of PrP(C), primarily using the chemical denaturant guanidine hydrochloride (GuHCl). When the protein conformation is assessed by NMR, there is a gradual shift of NMR signals in the regions between residues 125-146 and 186-196. The denaturant dependence of these shifts shows that in aqueous solution the native and locally unfolded conformations are both significantly populated. Following this shift, there is the major unfolding transition to generate a substantially unfolded population. However, analysis of NMR chemical shift and intensity changes shows that there is persistent structure in the molecule well beyond this major cooperative unfolding transition. Residual structure within this state is extensive and encompasses the majority of the secondary structure elements found in the native state of the protein. 相似文献
85.
86.
Hans Thordal-Christensen Ziguo Zhang Yangdou Wei David B. Collinge 《The Plant journal : for cell and molecular biology》1997,11(6):1187-1194
Active oxygen species (AOS) are believed to have important roles in plants in general and in plant—pathogen interactions in particular. They are believed to be involved in signal transduction, cell wall reinforcement, hypersensitive response (HR) and phytoalexin production, and to have direct antimicrobial effects. Since current methods are inadequate for localizing AOS in intact plant tissue, most studies have been conducted using cell suspension culture/elicitors systems. 3,3-diaminobenzidine (DAB) polymerizes instantly and locally as soon as it comes into contact with H2 O2 in the presence of peroxidase, and it was found that, by allowing the leaf to take up this substrate, in-vivo and in-situ detection of H2 O2 can be made at subcellular levels. This method was successfully used to detect H2 O2 in developing papillae and surrounding haloes (cell wall appositions) and whole cells of barley leaves interacting with the powdery mildew fungus. Thus, H2 O2 can be detected in the epidermal cell wall subjacent to the primary germ tube from 6 h after inoculation, and subjacent to the appressorium from 15 h. The earliest time point for observation of H2 O2 in relation to epidermal cells undergoing HR is 15 h after inoculation, first appearing in the zones of attachment to the mesophyll cells underneath, and eventually in the entire epidermal cell. Furthermore, it was observed that proteins in papillae and HR cells are cross-linked, a process believed to be fuelled by H2 O2 . This cross-linking reinforces the apposition, presumably assisting the arrest of the pathogen. 相似文献
87.
Summary We tested the hypothesis that light intensity was the direct, proximal mechanism causing significantly higher vulnerability
of Bittercress (Cardamine cordifolia A. Gray) clones in the sun to herbivory by a leaf-mining fly (Scaptomyza nigrita Wheeler). Clones in the sun were experimentally shaded. Plant performance and losses to leaf miners were compared to controls
in the sun and natural willow shade. Leaf-mining damage was significantly higher on artificially-shaded plants (P<0.01), opposite of our expectation. Shading sun plants shifted their growth pattern toward that of naturally-shaded plants.
No significant differences were detected in leaf water status or glucosinolate concentrations, eliminating water stress and
variation in defensive posture for mediating the between habitat differences in levels of herbivory. Although soluble sugars
varied significantly, they were higher in sun than either shade treatment. Total and free amino nitrogen concentrations were
highest in the artificially-shaded plants and lowest in naturally-occurring sun plants. Adult flies were more abundant on
sun and on artificially-shaded plants than on naturally-shaded plants. Thus, relative abundance of ovipositing flies in the
sun-exposed area, combined with the higher nitrogen availability in artificially-shaded plants, form the most plausible hypothesis
for factors mediating the experimentally documented pattern of herbivory. 相似文献
88.
A four generation backcross breeding program was undertaken. Analysis of the levels of cyanoglucoside in Acac progeny shows that the level of cyanoglucoside (linamarin and lotaustralin) is inherited and that part of the inherited variation in cyanoglucoside levels is attributable to the existence of different Ac alleles in the parent plant. In vitro microsomal cyanoglucoside biosynthetic activity was measured in a high-level and a low-level parent plant. There was no evidence for the presence of microsomes with different qualitative properties in the two plants. The Ac locus was shown to segregate independently of the S incompatibility locus.This research was supported in part by SERC Grant GRA 95550. 相似文献
89.
90.
Eric?Vallabh Minikel Inga Zerr Steven?J. Collins Claudia Ponto Alison Boyd Genevieve Klug André Karch Joanna Kenny John Collinge Leonel?T. Takada Sven Forner Jamie?C. Fong Simon Mead Michael?D. Geschwind 《American journal of human genetics》2014,95(4):371-382
Anticipation is the phenomenon whereby age of onset in genetic disease decreases in successive generations. Three independent reports have claimed anticipation in Creutzfeldt-Jakob disease (CJD) caused by the c.598G>A mutation in PRNP encoding a p.Glu200Lys (E200K) substitution in the prion protein. If confirmed, this finding would carry clear implications for genetic counseling. We analyzed pedigrees with this mutation from four prion centers worldwide (n = 217 individuals with the mutation) to analyze age of onset and death in affected and censored individuals. We show through simulation that selective ascertainment of individuals whose onset falls within the historical window since the mutation’s 1989 discovery is sufficient to create robust false signals both of anticipation and of heritability of age of onset. In our data set, the number of years of anticipation observed depends upon how strictly the data are limited by the ascertainment window. Among individuals whose disease was directly observed at a study center, a 28-year difference between parent and child age of onset is observed (p = 0.002), but including individuals ascertained retrospectively through family history reduces this figure to 7 years (p = 0.005). Applying survival analysis to the most thoroughly ascertained subset of data eliminates the signal of anticipation. Moreover, even non-CJD deaths exhibit 16 years anticipation (p = 0.002), indicating that ascertainment bias can entirely explain observed anticipation. We suggest that reports of anticipation in genetic prion disease are driven entirely by ascertainment bias. Guidelines for future studies claiming statistical evidence for anticipation are suggested. 相似文献