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111.
Rogier AM Quax Jan W Koper Pascal HP de Jong Ramona van Heerebeek Angelique E Weel Anne M Huisman Derkjen van Zeben Frank H de Jong Steven WJ Lamberts Johanna MW Hazes Richard A Feelders 《Arthritis research & therapy》2012,14(4):R195
Introduction
Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA.Methods
Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/KD) of glucocorticoid receptors (GRs).In vivo GC sensitivity was determined by measuring the disease activity score (DAS) and health assessment questionnaire disability index (HAQ-DI) score before and after 2 weeks of standardized GC treatment.Results
GR number was positively correlated with improvement in DAS. IL-2-EC50 and GILZ-EC50 values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC50 values and higher GR number and KD.Conclusions
Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA. 相似文献112.
113.
114.
Truus de Vrije Robert R Bakker Miriam AW Budde Man H Lai Astrid E Mars Pieternel AM Claassen 《Biotechnology for biofuels》2009,2(1):12-15
Background
The production of hydrogen from biomass by fermentation is one of the routes that can contribute to a future sustainable hydrogen economy. Lignocellulosic biomass is an attractive feedstock because of its abundance, low production costs and high polysaccharide content. 相似文献115.
Once thought to be impossible or a waste of resources, the initial high-volume stages of sequencing the human genome have been completed. 相似文献
116.
Leinweber B Parissenti AM Gallant C Gangopadhyay SS Kirwan-Rhude A Leavis PC Morgan KG 《The Journal of biological chemistry》2000,275(51):40329-40336
Previous studies from this laboratory have shown that, upon agonist activation, calponin co-immunoprecipitates and co-localizes with protein kinase Cepsilon (PKCepsilon) in vascular smooth muscle cells. In the present study we demonstrate that calponin binds directly to the regulatory domain of PKC both in overlay assays and, under native conditions, by sedimentation with lipid vesicles. Calponin was found to bind to the C2 region of both PKCepsilon and PKCalpha with possible involvement of C1B. The C2 region of PKCepsilon binds to the calponin repeats with a requirement for the region between amino acids 160 and 182. We have also found that calponin can directly activate PKC autophosphorylation. By using anti-phosphoantibodies to residue Ser-660 of PKCbetaII, we found that calponin, in a lipid-independent manner, increased auto-phosphorylation of PKCalpha, -epsilon, and -betaII severalfold compared with control conditions. Similarly, calponin was found to increase the amount of (32)P-labeled phosphate incorporated into PKC from [gamma-(32)P]ATP. We also observed that calponin addition strongly increased the incorporation of radiolabeled phosphate into an exogenous PKC peptide substrate, suggesting an activation of enzyme activity. Thus, these results raise the possibility that calponin may function in smooth muscle to regulate PKC activity by facilitating the phosphorylation of PKC. 相似文献
117.
Fear of humans is a source of stress for Holstein dairy cattle and can result when animals are handled aversively. We used aversion learning techniques to determine which handling practices cattle find most aversive. In an aversion race, the cows are repeatedly walked down a race and treatments applied when they reached the end; the time and force required for cows to walk down the race are measured. The animal learns to associate walking down the race with the treatment received; if the treatment is aversive, the animal will take more time and require more force to reach the end of the race than if the treatment is positive. In experiment 1, 54 cows were assigned to four treatments (hit/shout, brushing, control, and food). Treatments of 2-min duration were applied three times a day for 4 days. Cows on the hit/shout treatment took more time and required more force to walk through the race than cows on other treatments, while brushed cows took longer to move through the race than cows given food. In experiment 2, 60 cows were assigned to five treatments (electric prod, shouting, hitting, tail twist, and control). Treatments of 1-min duration were applied three times a day for 3 days. Cows on the shout and electric prod treatments took more time and required more force to walk down the race than cows on the control treatment. In experiment 3, thirty-six 1-1.5-year-old heifers were assigned to three treatments (hand feeding, gentling, or control) applied as in experiment 2. Treatments did not affect the time or force required to walk down the race. The aversion race successfully discriminated between handling treatments that differ greatly in aversiveness but lacked sensitivity to distinguish between treatments that were similar. Although many procedural factors must be considered, aversion learning techniques are an effective method to determine which handling practices cattle find aversive or rewarding. 相似文献
118.
Sunjin Moon Tae-Hun Kim Kyung-Tai Lee Woori Kwak Taeheon Lee Si-Woo Lee Myung-Jick Kim Kyuho Cho Namshin Kim Won-Hyong Chung Samsun Sung Taesung Park Seoae Cho Martien AM Groenen Rasmus Nielsen Yuseob Kim Heebal Kim 《BMC genomics》2015,16(1)
Background
Animal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication.Results
Whole-genome resequencing of 30 individual pigs from domesticated breeds, Landrace and Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting in over 4.3 million SNPs for 19,990 genes. We constructed a comprehensive genome map of directional selection by detecting selective sweeps using an FST-based approach that detects directional selection in lineages leading to the domesticated breeds and using a haplotype-based test that detects ongoing selective sweeps within the breeds. We show that candidate genes under selection are significantly enriched for loci implicated in quantitative traits important to pig reproduction and production. The candidate gene with the strongest signals of directional selection belongs to group III of the metabolomics glutamate receptors, known to affect brain functions associated with eating behavior, suggesting that loci under strong selection include loci involved in behaviorial traits in domesticated pigs including tameness.Conclusions
We show that a significant proportion of selection signatures coincide with loci that were previously inferred to affect phenotypic variation in pigs. We further identify functional enrichment related to behavior, such as signal transduction and neuronal activities, for those targets of selection during domestication in pigs.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1330-x) contains supplementary material, which is available to authorized users. 相似文献119.
LUÍSA C. CARVALHO JOÃO L. COITO SILVANA COLAÇO MAURÍCIO SANGIOGO SARA AMÂNCIO 《Plant, cell & environment》2015,38(4):777-789
Heat stress is a major limiting factor of grapevine production and quality. Acclimation and recovery are essential to ensure plant survival, and the recovery mechanisms can be independent of the heat response mechanisms. An experimental set up with and without acclimation to heat followed by recovery [stepwise acclimation and recovery (SAR) and stepwise recovery (SR), respectively] was applied to two grapevine varieties, Touriga Nacional (TN), and Trincadeira (TR), with different tolerance to abiotic stress. Major differences were found between leaves of SAR and SR, especially after recovery; in SAR, almost all parameters returned to basal levels while in SR they remained altered. Acclimation led to a swifter and short‐term antioxidative response, affecting the plant to a lesser extent than SR. Significant differences were found among varieties: upon stress, TN significantly increased ascorbate and glutathione reduction levels, boosting the cell's redox‐buffering capacity, while TR needed to synthesize both metabolites, its response being insufficient to keep the redox state at working levels. TR was affected by stress for a longer period and the up‐regulation pattern of antioxidative stress genes was more obvious. In TN, heat shock proteins were significantly induced, but the canonical heat‐stress gene signature was not evident probably because no shutdown of the housekeeping metabolism was needed. 相似文献
120.