Interleukin-17F (IL-17F), together with interleukin-17A (IL-17 or IL-17A), is a marker of T(H)17 cells, a new lineage of effector CD4(+) T cells to contribute to pathogenesis of a growing list of autoimmune and inflammatory diseases, such as experimental autoimmune encephalitis (EAE) and collagen-induced arthritis (CIA). IL-17F, similar to IL-17A, was reported to employ interleukin-17 receptor (IL-17R or IL-17RA) for signaling but the downstream cascades remain largely elusive. Here we report that TRAF6 interacts with IL-17R and mediates ubiquitination of the receptor. We observed that IL-17F and IL-17A could induce IL-17R ubiquitination and DN-TRAF6, a dominant-negative mutant, could block IL-17F- but not IL-17A-triggered ubiquitination of IL-17R. Moreover, we showed that the ubiquitination of IL-17R was positively correlated with the downstream signaling, as evaluated by a luciferase reporter driven by a putative native promoter of 24p3, an IL-17 targeted gene. Our results indicate that ubiquitination of IL-17R mediated by TRAF6 plays a critical role in IL-17F signaling. This study, for the first time, reveals a possible molecular mechanism that the initiation of the IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. 相似文献
Pollen map data at 2000-year intervals are used to reconstruct changes in Holocene forest cover in China north of the Yangtze
River. In almost all regions, the early Holocene from 10 ka b.p. to 6 ka b.p. is characterised by an increase in forest cover although there was a reversal to lower forest cover at 8 ka b.p. in the eastern monsoon regions. A maximum of forest cover was reached at 6 ka b.p. in all regions except for Northeast China where forest cover peaked in the late Holocene. All regions except for Northeast
China experienced a marked decline in forest cover after 6 ka b.p. Since 6 ka b.p., forest cover has decreased by about 92% in the middle and lower reaches of the Yellow River, 64% in the easternmost part
of the Qinghai-Tibet Plateau and 37% between the Yangtze River and the Huaihe River. In contrast, forest cover in Northeast
China increased significantly from 6 ka b.p., but has declined between 2 ka b.p. and the present. Changes in forest cover prior to 6 ka b.p. were probably caused by climate, but the evident drop in forest cover since that time in most regions may have been induced
predominantly by human activities. 相似文献
In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis
(RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the
HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies
of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and
24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL
at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the
diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS
cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores
compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab
and placebo groups was similar in the AS (10.1, 9.2–11.0), PsA (8.6, 7.8–9.4), and RA (10.1, 9.2–11.0) cohorts. Patients with
RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those
in the placebo group with an effect size of 4.6 (4.2–5.1) in RA and 2.7 (2.4–3.1) in PsA. Patients in large randomized controlled
studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly
greater improvement in HRQoL after treatment with infliximab. 相似文献
A high throughput screening was carried out in order to search for inhibitors of acetylcholinesterase (AChE) from microorganism metabolites. An actinomycete strain was found to produce active compounds named N98-1272 A, B and C with IC50 of 15.0, 11.5, 12.5 microM, respectively. Structural studies revealed that the three compounds are identical to the known antibiotics, Manumycin C, B and A. Kinetic analyses showed that N98-1272 C (Manumycin A) acted as a reversible noncompetitive inhibitor of acetylcholinesterase, with a Ki value of 7.2 microM. The cyclohexenone epoxide part of the structure plays a crucial role in the inhibitory activity against AChE. Compared with Tacrine, N98-1272 A, B, and C exhibit much better selectivity toward AChE over BuChE. 相似文献
Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner. 相似文献
A Gram-staining-positive, non-spore-forming, non-flagellated, ellipsoidal, strain Z1-20 T belonging to the genus Arthrobacter was isolated from a soil sample collected from the Zhongshan station, Antarctic. Phylogenetic analysis of the 16S rRNA gene sequences and phylogenetic analysis revealed that strain Z1-20 T formed a unique single cluster in the genus Arthrobacter and shared high 16S rRNA sequence similarities of 97.1% and 96.9% with A. glacialis HLT2-12-2 T and A. psychrochitiniphilus GP3T, respectively. Values of Digital DNA-DNA hybridization (dDDH) between strain Z1-20 T against A. glacialis HLT2-12-2 T and A. psychrochitiniphilus GP3T were 20.3% and 13.8%, respectively. Average nucleotide identity (ANI) score between strain Z1-20 T against A. glacialis HLT2-12-2 T and A. psychrochitiniphilus GP3T were 72.5% and 72.1%, respectively. Genes for the synthesis of the osmoprotectant glycine betaine and higher copies of capA gene encoding cold shock protein were found in genome of Z1-20 T that may help Z1-20 T in cold-adaptation. Strain Z1-20 T comprised lysine as the diagnostic diamino acid. Based on the results of phylogenetic, phenotypic and chemotaxonomic features, strain Z1-20 T represents a novel species of a novel taxon of genus Arthrobacter, for which the name Arthrobacter terrae gen. nov., sp. nov. is proposed.
Dehydrins (DHNs) as the member of the late embryogenesis abundant protein family, play critical roles in seed dehydration protection and plant adaptation to multiple abiotic stresses. As an important method of germplasm preservation, cryopreservation is also an ideal research system to study compound stress. Oxidative stress, as the critical stress in cryopreservation, directly affects cell viability. Our previous in vitro tests indicated that ApY2SK2 DHN can effectively protect enzyme activity and almost double the survival rate of Arabidopsis thaliana seedlings after cryopreservation, but the in vivo protective effect of ApY2SK2 on cryopreservation have not yet been elucidated. In this study, ApY2SK2 type DHN was genetically transformed into embryogenic callus (EC) of Agapanthus praecox by overexpression (OE) and RNA interference (RNAi) techniques to evaluate the in vivo oxidative stress protective effect of DHNs during cryopreservation. The results showed that the cell viability had a completely opposite trend between OE and RNAi cell lines, and the cell relative death ratio of ApY2SK2-OE EC was significantly decreased 18.5% and ApY2SK2-RNAi cells was significantly increased 23.5% after cryopreservation. Overexpression ApY2SK2 increased non-enzymatic antioxidant (AsA and GSH) contents, antioxidant enzyme (POD and SOD) activities and up-regulated CAT, POD and GPX expression, while ApY2SK2-RNAi cells decreased CAT, FeSOD, POD and GPX expression during cryopreservation. These findings suggested that ApY2SK2 can affect ROS metabolism, alleviate H2O2 and OH·excessive generation, activate the antioxidant system, improve cellular REDOX balance and reduce membrane lipid peroxidation damage of plant cells during cryopreservation. DHNs can effectively improve cell stress tolerance and have great potential for in vivo or in vitro applications in plant cryopreservation.
Plant Growth Regulation - Anthocyanidin synthase (ANS) is involved in the synthesis of anthocyanins, which are important phytonutrients because of their beneficial effects on human health. Here, we... 相似文献
Journal of Plant Growth Regulation - Gibberellin (GA), auxin (IAA) and brassinosteroid (BR) are indispensable in the process of plant growth and development. Currently, research on the regulatory... 相似文献
Molecular and Cellular Biochemistry - Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher... 相似文献