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41.
Martinus AM van Boekel Erik R Vossenaar Frank HJ van den Hoogen Walther J van Venrooij 《Arthritis research & therapy》2001,3(2):1-7
This review focuses on the mechanisms of stress response in the synovial tissue of rheumatoid arthritis. The major stress factors, such as heat stress, shear stress, proinflammatory cytokines and oxidative stress, are discussed and reviewed, focusing on their potential to induce a stress response in the synovial tissue. Several pathways of stress signalling molecules are found to be activated in the synovial membrane of rheumatoid arthritis; of these the most important examples are heat shock proteins, mitogen-activated protein kinases, stress-activated protein kinases and molecules involved in the oxidative stress pathways. The expression of these pathways in vitro and in vivo as well as the consequences of stress signalling in the rheumatoid synovium are discussed. Stress signalling is part of a cellular response to potentially harmful stimuli and thus is essentially involved in the process of synovitis. Stress signalling pathways are therefore new and promising targets of future anti-rheumatic therapies. 相似文献
42.
Background
Over the last ten years, genomic selection has developed enormously. Simulations and results on real data suggest that breeding values can be predicted with high accuracy using genetic markers alone. However, to reach high accuracies, large reference populations are needed. In many livestock populations or even species, such populations cannot be established when traits are difficult or expensive to record, or when the population size is small. The value of genomic selection is then questionable.Methods
In this study, we compare traditional breeding schemes based on own performance or progeny information to genomic selection schemes, for which the number of phenotypic records is limiting. Deterministic simulations were performed using selection index theory. Our focus was on the equilibrium response obtained after a few generations of selection. Therefore, we first investigated the magnitude of the Bulmer effect with genomic selection.Results
Results showed that the reduction in response due to the Bulmer effect is the same for genomic selection as for selection based on traditional BLUP estimated breeding values, and is independent of the accuracy of selection. The reduction in response with genomic selection is greater than with selection based directly on phenotypes without the use of pedigree information, such as mass selection. To maximize the accuracy of genomic estimated breeding values when the number of phenotypic records is limiting, the same individuals should be phenotyped and genotyped, rather than genotyping parents and phenotyping their progeny. When the generation interval cannot be reduced with genomic selection, large reference populations are required to obtain a similar response to that with selection based on BLUP estimated breeding values based on own performance or progeny information. However, when a genomic selection scheme has a moderate decrease in generation interval, relatively small reference population sizes are needed to obtain a similar response to that with selection on traditional BLUP estimated breeding values.Conclusions
When the trait of interest cannot be recorded on the selection candidate, genomic selection schemes are very attractive even when the number of phenotypic records is limited, because traditional breeding requires progeny testing schemes with long generation intervals in those cases. 相似文献43.
44.
Molecular evidence for the rapid propagation of mouse t haplotypes from a single, recent, ancestral chromosome 总被引:11,自引:0,他引:11
Silver LM; Hammer M; Fox H; Garrels J; Bucan M; Herrmann B; Frischauf AM; Lehrach H; Winking H; Figueroa F 《Molecular biology and evolution》1987,4(5):473-482
Mouse t haplotypes are variant forms of chromosome 17 that exist at high
frequencies in worldwide populations of two species of commensal mice. To
determine both the relationship of t haplotypes to each other and the
species within which they exist, 35 representative t haplotypes were
analyzed by means of 10 independent molecular probes, including five DNA
clones and five polypeptide spots identified by means of two- dimensional
gel electrophoresis. All of the tested haplotypes were found to share
restriction fragments and polypeptide spots that are absent in mice
carrying wild-type forms of chromosome 17. This observation provides the
first direct evidence that all of the known t haplotypes are descendents of
a single ancestral chromosome. The absence of variation among t haplotypes
could mean that this ancestral chromosome existed relatively recently, in
which case it would be necessary to postulate introgressions of t
haplotypes across species lines to explain their presence in both Mus
domesticus and M. musculus. Alternatively, it is possible that the
ancestral chromosome existed prior to the split between M. domesticus and
M. musculus and that, by chance, our probes fail to detect polymorphisms
that exist among the t haplotypes. A further result of our analysis is the
characterization of a partial t haplotype in a wild population of Israeli
mice.
相似文献
45.
Background
In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical significance testing for an alignment. The e-value is the most commonly used statistical validation method for sequence database searching. The CluSTr database and the Protein World database have been created using an alternative statistical significance test: a Z-score based on Monte-Carlo statistics. Several papers have described the superiority of the Z-score as compared to the e-value, using simulated data. We were interested if this could be validated when applied to existing, evolutionary related protein sequences. 相似文献46.
47.
In a simulation study different designs for a pure line pig population were compared for efficiency of mapping QTL using the variance component method. Phenotypes affected by a Mendelian QTL, a paternally expressed QTL, a maternally expressed QTL or by a QTL without an effect were simulated. In all alternative designs 960 progeny were phenotyped. Given the limited number of animals there is an optimum between the number of families and the family size. Estimation of Mendelian and parentally expressed QTL is more efficient in a design with large family sizes. Too small a number of sires should be avoided to minimize chances of sires to be non-segregating. When a large number of families is used, the number of haplotypes increases which reduces the accuracy of estimating the QTL effect and thereby reduces the power to show a significant QTL and to correctly position the QTL. Dense maps allow for smaller family size due to exploitation of LD-information. Given the different possible modes of inheritance of the QTL using 8 to16 boars, two litters per dam was optimal with respect to determining significance and correct location of the QTL for a data set consisting of 960 progeny. The variance component method combining linkage disequilibrium and linkage analysis seems to be an appropriate choice to analyze data sets which vary in marker density and which contain complex family structures. 相似文献
48.
Seventy-three patients were studied after ingesting a liquid glucose meal, tagged with 113Indium. Nineteen of these patients were awaiting surgery for their duodenal ulcer, while 54 were studied postoperatively, 25 of whom experienced troublesome postprandial (dumping) symptoms in their daily lives. The radioactive marker emptied significantly faster in the symptomatic patients than in the symptomfree, pre and post-operative groups (initial emptying rate 3.45 ± 0.23, compared with 1.16 ± 0.19 and 1.27 ± 0.15% fall in counts/min respectively; p < 0.01). Initial (20 min) rises in the plasma concentrations of neurotensin-like immunoreactivity measured during the test correlated significantly with the rate of gastric emptying in all patients, being greatest in patients with dumping symptoms. Physiological concentrations of neurotensin have been shown to delay gastric emptying. The excessive rise in plasma neurotensin-like immunoreactivity in patients with dumping symptoms, presumably occuring as a result of the rapid passage of nutrients to the neurotensin-rich ileum, may possibly have a compensatory role in slowing further emptying from the stomach. 相似文献
49.
50.
Annette AM Gerritsen Rob JPM Scholten Willem JJ Assendelft Herman Kuiper Henrica CW de Vet Lex M Bouter 《BMC neurology》2001,1(1):8-7