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101.
Underwood CK Coulson EJ 《The international journal of biochemistry & cell biology》2008,40(9):1664-1668
The pan neurotrophin receptor (p75(NTR)) is best known for mediating neural cell death during development as well as in the adult following injury, the latter making it a target for the treatment of neurodegenerative disease. Although p75(NTR) has been studied for over 30 years, a number of recent discoveries have changed our understanding of its regulation. Here we provide a brief overview of the p75(NTR) protein, its post-translational modifications, and the phenotype of p75(NTR)-deficient mice as a starting point for researchers unfamiliar with this complex receptor. The accepted mechanisms underlying the ability of p75(NTR) to regulate cell death as well as a number of other neural functions, most notably neuronal differentiation, neurite outgrowth and synaptic plasticity, are also summarised. 相似文献
102.
Ecological consequences of genetic diversity 总被引:4,自引:0,他引:4
Understanding the ecological consequences of biodiversity is a fundamental challenge. Research on a key component of biodiversity, genetic diversity, has traditionally focused on its importance in evolutionary processes, but classical studies in evolutionary biology, agronomy and conservation biology indicate that genetic diversity might also have important ecological effects. Our review of the literature reveals significant effects of genetic diversity on ecological processes such as primary productivity, population recovery from disturbance, interspecific competition, community structure, and fluxes of energy and nutrients. Thus, genetic diversity can have important ecological consequences at the population, community and ecosystem levels, and in some cases the effects are comparable in magnitude to the effects of species diversity. However, it is not clear how widely these results apply in nature, as studies to date have been biased towards manipulations of plant clonal diversity, and little is known about the relative importance of genetic diversity vs. other factors that influence ecological processes of interest. Future studies should focus not only on documenting the presence of genetic diversity effects but also on identifying underlying mechanisms and predicting when such effects are likely to occur in nature. 相似文献
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105.
Diatom biofilms are abundant in the marine environment. It is assumed (but untested) that extracellular polymeric substances (EPS), produced by diatoms, enable cells to cope with fluctuating salinity. To determine the protective role of EPS, Cylindrotheca closterium was grown in xanthan gum at salinities of 35, 50, 70 and 90 ppt. A xanthan matrix significantly increased cell viability (determined by SYTOX-Green), growth rate and population density by up to 300, 2,300 and 200%, respectively. Diatoms grown in 0.75% w/v xanthan, subjected to acute salinity shock treatments (at salinities 17.5, 50, 70 and 90 ppt) maintained photosynthetic capacity, Fq′/Fm′, within 4% of pre-shock values, whereas Fq′/Fm′ in cells grown without xanthan declined by up to 64% with hypersaline shock. Biofilms that developed in xanthan at standard salinity helped cells to maintain function during salinity shock. These results provide evidence of the benefits of living in an EPS matrix for biofilm diatoms. 相似文献
106.
Hanna W van Steenbergen Jessica AB van Nies Tom WJ Huizinga Monique Reijnierse Annette HM van der Helm-van Mil 《Arthritis research & therapy》2014,16(2):R92
Introduction
It is known that anticitrullinated peptide antibody (ACPA)–positive rheumatoid arthritis (RA) has a preclinical phase. Whether this phase is also present in ACPA-negative RA is unknown. To determine this, we studied ACPA-negative arthralgia patients who were considered prone to progress to RA for local subclinical inflammation observed on hand and foot magnetic resonance imaging (MRI) scans.Methods
We studied a total of 64 ACPA-negative patients without clinically detectable arthritis and with arthralgia of the small joints within the previous 1 year. Because of the character of the patients’ symptoms, the rheumatologists considered these patients to be prone to progress to RA. For comparisons, we evaluated 19 healthy, symptom-free controls and 20 ACPA-negative RA patients, who were identified according to the 1987 American Rheumatism Association criteria. All participants underwent MRI of unilateral wrist, metacarpophalangeal and metatarsophalangeal joints. Synovitis and bone marrow oedema (BME) were scored according to the OMERACT rheumatoid arthritis magnetic resonance imaging scoring system, and the scores were summed to yield the ‘MRI inflammation score’. Scores were compared between groups. Among the ACPA-negative arthralgia patients, MRI inflammation scores were related to C-reactive protein (CRP) levels and the tenderness of scanned joints.Results
MRI inflammation scores increased progressively among the groups of controls and ACPA-negative arthralgia and RA patients (median scores = 0, 1 and 10, respectively; P < 0.001). The MRI inflammation scores of ACPA-negative arthralgia patients were significantly higher than those of controls (P = 0.018). In particular, the synovitis scores were higher in ACPA-negative arthralgia patients (P = 0.046). Among the ACPA-negative arthralgia patients, inflammation was observed predominantly in the wrist (53%). The synovitis scores were associated with CRP levels (P = 0.007) and joint tenderness (P = 0.026). Despite the limited follow-up duration, five patients developed clinically detectable arthritis. These five patients had higher scores for MRI inflammation (P = 0.001), synovitis (P = 0.002) and BME (P = 0.003) compared to the other patients.Conclusion
Subclinical synovitis was observed in the small joints of ACPA-negative arthralgia patients, and especially in patients whose conditions progressed to clinically detectable arthritis. This finding suggests the presence of a preclinical phase in ACPA-negative RA. Further longitudinal studies of these lesions and patients are required to confirm this hypothesis. 相似文献107.
Rachel Knevel Diederik PC de Rooy Tore Saxne Elisabet Lindqvist Martha K Leijsma Nina A Daha Bobby PC Koeleman Roula Tsonaka Jeanine J Houwing-Duistermaat Joris JM Schonkeren Rene EM Toes Tom WJ Huizinga Elisabeth Brouwer Anthony G Wilson Annette HM van der Helm-van Mil 《Arthritis research & therapy》2014,16(3):R108
Introduction
Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA.Methods
1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied.Results
We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P = 2.35x10−4). This variant was also significant after Bonferroni correction.Conclusions
These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA. 相似文献108.
109.
Antigen valency has been defined (Singer, 1965) as the maximum number of epitopes per antigen which can be simultaneously occupied by antibody. If the epitopes are closely spaced, steric hindrance prevents the simultaneous occupancy of all epitopes. Current methods of estimating both the antigen valency and the association constant (Ka) from equilibrium binding data do not allow for the effects of steric hindrance. We have developed a theory which accounts rigorously for steric hindrance when monovalent ligands of quite general shape (antibodies) react reversibly with multivalent acceptor molecules (antigens). The surfaces of the acceptors are modelled by completely general two-dimensional lattices. Using this theory we demonstrate that curvature of Scatchard plots can arise from steric effects alone in the absence of other known causes such as cross-linking, cooperativity and heterogeneous epitope affinities. Our results generalize the conclusions of McGhee & von Hippel (1974) who dealt with one-dimension acceptor molecules such as DNA. We discuss inaccuracies in the estimation of both Ka and antigen valency using the traditional approach of fitting straight lines to Scatchard plots. 相似文献
110.
Mattias Ljunggren Karin Willquist Guido Zacchi Ed WJ van Niel 《Biotechnology for biofuels》2011,4(1):1-15