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51.
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
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53.
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54.
55.
D A Myles S A Rule L J DeLucas Y S Babu Y Xu J E Volanakis C E Bugg S Bailey T J Greenhough 《Journal of molecular biology》1990,216(3):491-496
Rotation function studies of two tetragonal crystal forms of human C-reactive protein have confirmed the pentameric structure of the molecule. The two crystal forms have space groups P4122 (I) and P4222 (II) with closely similar unit cells and are often twinned together. Investigation of the crystallization conditions indicates that dissociation heterogeneity has been a major limiting factor in the reproducible growth of good single crystals. The orientation of the pentameric molecule is shown to be almost identical in both forms, about the axial direction omega = 57 degrees, phi = 45 degrees, i.e. 57 degrees away from c in the (110) plane. 相似文献
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57.
Pierre Delanaye Richard J. Glassock Hans Pottel Andrew D. Rule 《The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists》2016,37(1):17-26
Defining chronic kidney disease (CKD) is the subject of intense debate in the current nephrology literature. The debate concerns the threshold value of estimated glomerular filtration rate (eGFR) used to make the diagnosis of CKD. Current recommendations argue that a universal threshold of 60 mL/min/1.73m2 should be used. This threshold has been defended by epidemiological studies showing that the risk of mortality or end-stage renal disease increases with an eGFR below 60 mL/min/1.73m2. However, a universal threshold does not take into account the physiologic decline in GFR with ageing nor does it account for the risk of mortality and end-stage renal disease being trivial with isolated eGFR levels just below 60 mL/min/1.73m2 in older subjects and significantly increased with eGFR levels just above 60 mL/min/1.73m2 among younger patients. Overestimation of the CKD prevalence in the elderly (medicalisation of senescence) and underestimation of CKD (potentially from treatable primary nephrologic diseases) in younger patients is of primary concern. An age-calibrated definition of CKD has been proposed to distinguish age-related from disease-related changes in eGFR. For patients younger than 40 years, CKD is defined by eGFR below 75 mL/min/1.73m2. For patients with ages between 40 and 65 years, CKD is defined by 60 mL/min/1.73m2. For subjects older than 65 years without albuminuria or proteinuria, CKD is defined by eGFR below 45 mL/min/1.73m2. 相似文献
58.
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
59.
L J DeLucas T J Greenhough S A Rule D A Myles Y S Babu J E Volanakis C E Bugg 《Journal of molecular biology》1987,196(3):741-742
Two different crystal forms of human C-reactive protein have been grown from solutions of 2-methyl-2,4-pentanediol. Both crystal forms are tetragonal, the space group for form I is P4(1)22 (or P4(3)22), and that for form II is P4(2)22. The unit cell parameters for form I are a = b = 103.0(5) A, c = 308.5(7) A and for form II are a = b = 103.1(2) A, c = 312.7(6) A. The crystals of form II diffract to at least 3.0 A resolution, and are suitable for detailed structural studies. 相似文献
60.