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21.
Introduction
Recent evidence suggests that intervertebral disc (IVD) cells derived from degenerative tissue are unable to respond to physiologically relevant mechanical stimuli in the 'normal' anabolic manner, but instead respond by increasing matrix catabolism. Understanding the nature of the biological processes which allow disc cells to sense and respond to mechanical stimuli (a process termed 'mechanotransduction') is important to ascertain whether these signalling pathways differ with disease. The aim here was to investigate the involvement of interleukin (IL)-1 and IL-4 in the response of annulus fibrosus (AF) cells derived from nondegenerative and degenerative tissue to cyclic tensile strain to determine whether cytokine involvement differed with IVD degeneration. 相似文献22.
The Tapora Landcare Group, operating on the Okahukura Peninsula, has the long-term goal of making this region predator fenced. The aim of this study was to obtain information on the current status of avian biodiversity and the bird community across the band of coastal wetlands on the Okahukura Peninsula. Bird counts were conducted and playback lures used to detect three cryptic wetland species: fernbirds (Bowdleria punctata); spotless crakes (Porzana tabuensis); and banded rails (Gallirallus philippensis). Fernbirds and banded rails were detected at seven of the eight wetland sites sampled whereas spotless crakes were detected at two sites. The native species with the highest relative abundance across the eight sites were silvereyes (Zosterops lateralis) and South Island pied oystercatchers (Haematopus finschi). Changes in avian biodiversity over time in the region can now be monitored, and comprehensive long-term data on the status of avian biodiversity over time obtained. 相似文献
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Glynn Dennis Jr Cécile TJ Holweg Sarah K Kummerfeld David F Choy A Francesca Setiadi Jason A Hackney Peter M Haverty Houston Gilbert Wei Yu Lin Lauri Diehl S Fischer An Song David Musselman Micki Klearman Cem Gabay Arthur Kavanaugh Judith Endres David A Fox Flavius Martin Michael J Townsend 《Arthritis research & therapy》2014,16(2):R90
Introduction
Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Currently, the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood.Methods
We analyzed synovial tissue samples from two RA cohorts of 49 and 20 patients using a combination of global gene expression, histologic and cellular analyses, and analysis of gene expression data from two further publicly available RA cohorts. To identify candidate serum biomarkers that correspond to differential synovial biology and clinical response to targeted therapies, we performed pre-treatment biomarker analysis compared with therapeutic outcome at week 24 in serum samples from 198 patients from the ADACTA (ADalimumab ACTemrA) phase 4 trial of tocilizumab (anti-IL-6R) monotherapy versus adalimumab (anti-TNFα) monotherapy.Results
We documented evidence for four major phenotypes of RA synovium – lymphoid, myeloid, low inflammatory, and fibroid - each with distinct underlying gene expression signatures. We observed that baseline synovial myeloid, but not lymphoid, gene signature expression was higher in patients with good compared with poor European league against rheumatism (EULAR) clinical response to anti-TNFα therapy at week 16 (P =0.011). We observed that high baseline serum soluble intercellular adhesion molecule 1 (sICAM1), associated with the myeloid phenotype, and high serum C-X-C motif chemokine 13 (CXCL13), associated with the lymphoid phenotype, had differential relationships with clinical response to anti-TNFα compared with anti-IL6R treatment. sICAM1-high/CXCL13-low patients showed the highest week 24 American College of Rheumatology (ACR) 50 response rate to anti-TNFα treatment as compared with sICAM1-low/CXCL13-high patients (42% versus 13%, respectively, P =0.05) while anti-IL-6R patients showed the opposite relationship with these biomarker subgroups (ACR50 20% versus 69%, P =0.004).Conclusions
These data demonstrate that underlying molecular and cellular heterogeneity in RA impacts clinical outcome to therapies targeting different biological pathways, with patients with the myeloid phenotype exhibiting the most robust response to anti-TNFα. These data suggest a path to identify and validate serum biomarkers that predict response to targeted therapies in rheumatoid arthritis and possibly other autoimmune diseases.Trial registration
ClinicalTrials.gov NCT01119859相似文献24.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
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Marleen TJ van Ampting Arjan J Schonewille Carolien Vink Robert Jan M Brummer van der Roelof Meer Ingeborg MJ Bovee-Oudenhoven 《BMC physiology》2009,9(1):6-9
Background
Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation. 相似文献28.
To study whether absolute (m/s) or relative (body lengths/s) speed should be used to compare the vulnerability of differently sized animals, we developed a simple computer simulation. Human 'predators' were asked to 'catch' (mouse-click) prey of different sizes, moving at different speeds across a computer screen. Using the simulation, a prey's chances of escaping predation depended on its speed (faster prey were more difficult to catch than slower prey of the same body size), but also on its size (larger prey were easier to catch than smaller prey at the same speed). Catching time, the time needed to catch a prey, also depended on both prey speed and prey size. Relative prey speed (body lengths/s or body surface/s) was a better predictor of catching time than was absolute prey speed (m/s). Our experiment demonstrates that, in contrast to earlier assertions, per unit body length speed of prey may be more 'ecologically relevant' than absolute speed. Copyright 1998 The Association for the Study of Animal Behaviour. 相似文献
29.
Octodon degus, a social hystricomorph rodent, responds to olfactory cues from a gonadally intact female entrained to a light-dark cycle (LD) by accelerating reentrainment of running wheel activity following a 6-h phase advance of the LD cycle. In this study, we examined the role of ovarian hormones in the production of and responsiveness to olfactory social cues in females. Experiment 1: intact females were sequentially phase-advanced 6 h with photic cues alone, or in the presence of an intact female donor, ovariectomized (OVX) donor, a castrated male, or a castrated male with testosterone replacement. Acceleration of reentrainment occurred only in the presence of the intact female donor while reentrainment was delayed by OVX donors. Experiment 2: OVX females undergoing a 6-h phase advance did not accelerate reentrainment in the presence of an intact female donor compared to reentrainment with photic cues alone. Thus, ovarian hormones are necessary for both the production of and responsiveness to olfactory cues. Experiment 3: OVX females implanted with estrogen-filled Silastic capsules did not accelerate reentrainment following the 6-h phase advance in the presence of an intact donor, whereas animals implanted with a combination of estrogen- and progesterone-filled capsules (Experiment 4) reduced the length of time needed to reentrain in the presence of an intact donor. Therefore, combined progesterone and estrogen are sufficient for responsiveness to the effective olfactory cue in intact donor females. These data clarify that the sex difference in sensitivity to non-photic odor effects on circadian reentrainment is caused by both the testosterone's inhibitory effects (Octodon degus. J. Biol. Rhythms 18 (2003) 43-50) and the enhancing effects of progesterone and estrogen. 相似文献
30.
The phylogenetic position of the Pedetidae, represented by a single species
Pedetes capensis, is controversial, reflecting in part the retention of
both Hystricomorphous and Sciurognathous characteristics in this rodent. In
an attempt to clarify the species evolutionary relationships, mtDNA gene
sequences from 10 rodent species (representing seven families) were
analyzed using phenetic, parsimony, and maximum-likelihood methods of
phylogenetic inference; the rabbit, Oryctolagus cuniculus (Order
Lagomorpha), and cow, Bos taurus (Order Artiodactyla), were used as
outgroups. Investigation of 714 base pairs of the protein-coding cytochrome
b gene indicate strong base bias at the third codon position with
significant rate heterogeneity evident between the three structural domains
of this gene. Similar analyses conducted on 816 base pairs of the 12S rRNA
gene revealed a transversion bias in the loop sections of all taxa. The
cytochrome b gene sequences proved useful in resolving associations between
closely related species but failed to produce consistent tree topologies at
the family level. In contrast, phylogenetic analysis of the 12S rRNA gene
resulted in strong support for the clustering of
Pedetidae/Heteromyidae/Geomyidae and Muridae in one clade to the exclusion
of the Hystricidae/Thryonomyidae and Sciuridae, a finding which is
concordant with studies of rodent fetal membranes as well as reproductive
and other anatomical features.
相似文献