排序方式: 共有79条查询结果,搜索用时 93 毫秒
51.
Meimaridou E Kowalczyk J Guasti L Hughes CR Wagner F Frommolt P Nürnberg P Mann NP Banerjee R Saka HN Chapple JP King PJ Clark AJ Metherell LA 《Nature genetics》2012,44(7):740-742
Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands. 相似文献
52.
Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete inflammatory arthropathies 总被引:1,自引:1,他引:0
Nikolett Marton Orsolya Tünde Kovács Eszter Baricza Ágnes Kittel Dávid Győri Attila Mócsai Florian M. P. Meier Carl S. Goodyear Iain B. McInnes Edit I. Buzás György Nagy 《Cellular and molecular life sciences : CMLS》2017,74(19):3599-3611
Objective
Extracellular vesicles (EVs) are subcellular signalosomes. Although characteristic EV production is associated with numerous physiological and pathological conditions, the effect of blood-derived EVs on bone homeostasis is unknown. Herein we evaluated the role of circulating EVs on human osteoclastogenesis.Methods
Blood samples from healthy volunteers, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based EV sub-fractions were isolated by gravity-driven filtration and differential centrifugation. To investigate the properties of EV samples, resistive pulse sensing technique, transmission electron microscopy, flow cytometry and western blot were performed. CD14+ monocytes were separated from PBMCs, and stimulated with recombinant human M-CSF, RANKL and blood-derived EV sub-fractions. After 7 days, the cells were fixed and stained for tartrate-resistant acid phosphatase and counted.Results
EVs isolated by size-based sub-fractions were characterized as either microvesicles or exosomes (EXO). Healthy (n = 11) and RA-derived (n = 12) EXOs profoundly inhibited osteoclast differentiation (70%, p < 0.01; 65%, p < 0.01, respectively). In contrast, PsA-derived (n = 10) EXOs had a stimulatory effect (75%, p < 0.05). In cross-treatment experiments where EXOs and CD14+ cells were interchanged between the three groups, only healthy (n = 5) and RA (n = 5)-derived EXOs inhibited (p < 0.01, respectively) the generation of osteoclasts in all groups, whereas PsA (n = 7)-derived EXOs were unable to mediate this effect.Conclusions
Our data suggest that blood-derived EXOs are novel regulators of the human osteoclastogenesis and may offer discrete effector function in distinct inflammatory arthropathies.53.
54.
Stadler MB Murr R Burger L Ivanek R Lienert F Schöler A van Nimwegen E Wirbelauer C Oakeley EJ Gaidatzis D Tiwari VK Schübeler D 《Nature》2011,480(7378):490-495
55.
This paper develops a dynamic factor model that uses euro area country-specific information on output and inflation to estimate an area-wide measure of the output gap. Our model assumes that output and inflation can be decomposed into country-specific stochastic trends and a common cyclical component. Comovement in the trends is introduced by imposing a factor structure on the shocks to the latent states. We moreover introduce flexible stochastic volatility specifications to control for heteroscedasticity in the measurement errors and innovations to the latent states. Carefully specified shrinkage priors allow for pushing the model towards a homoscedastic specification, if supported by the data. Our measure of the output gap closely tracks other commonly adopted measures, with small differences in magnitudes and timing. To assess whether the model-based output gap helps in forecasting inflation, we perform an out-of-sample forecasting exercise. The findings indicate that our approach yields superior inflation forecasts, both in terms of point and density predictions. 相似文献
56.
Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions 总被引:10,自引:0,他引:10
Winkelmann J Schormair B Lichtner P Ripke S Xiong L Jalilzadeh S Fulda S Pütz B Eckstein G Hauk S Trenkwalder C Zimprich A Stiasny-Kolster K Oertel W Bachmann CG Paulus W Peglau I Eisensehr I Montplaisir J Turecki G Rouleau G Gieger C Illig T Wichmann HE Holsboer F Müller-Myhsok B Meitinger T 《Nature genetics》2007,39(8):1000-1006
57.
Schormair B Kemlink D Roeske D Eckstein G Xiong L Lichtner P Ripke S Trenkwalder C Zimprich A Stiasny-Kolster K Oertel W Bachmann CG Paulus W Högl B Frauscher B Gschliesser V Poewe W Peglau I Vodicka P Vávrová J Sonka K Nevsimalova S Montplaisir J Turecki G Rouleau G Gieger C Illig T Wichmann HE Holsboer F Müller-Myhsok B Meitinger T Winkelmann J 《Nature genetics》2008,40(8):946-948
We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda corrected) = 5.91 x 10(-10), odds ratio (OR) = 1.44; rs1975197, P(nominal/lambda corrected) = 5.81 x 10(-9), OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS. 相似文献
58.
Ahmed Lawan Hao Shi Florian Gatzke Anton M. Bennett 《Cellular and molecular life sciences : CMLS》2013,70(2):223-237
The balance of protein phosphorylation is achieved through the actions of a family of protein serine/threonine kinases called the mitogen-activated protein kinases (MAPKs). The propagation of MAPK signals is attenuated through the actions of the MAPK phosphatases (MKPs). The MKPs specifically inactivate the MAPKs by direct dephosphorylation. The archetypal MKP family member, MKP-1 has garnered much of the attention amongst its ten other MKP family members. Initially viewed to play a redundant role in the control of MAPK signaling, it is now clear that MKP-1 exerts profound regulatory functions on the immune, metabolic, musculoskeletal and nervous systems. This review focuses on the physiological functions of MKP-1 that have been revealed using mouse genetic approaches. The implications from studies using MKP-1-deficient mice to uncover the role of MKP-1 in disease will be discussed. 相似文献
59.
Caitlin Collin Frank Hauser Ernesto Gonzalez de Valdivia Shizhong Li Julia Reisenberger Eva M. M. Carlsen Zaid Khan Niels Ø. Hansen Florian Puhm Leif Søndergaard Justyna Niemiec Magdalena Heninger Guilin R. Ren Cornelis J. P. Grimmelikhuijzen 《Cellular and molecular life sciences : CMLS》2013,70(21):4197-4197
60.
P Dutta G Courties Y Wei F Leuschner R Gorbatov CS Robbins Y Iwamoto B Thompson AL Carlson T Heidt MD Majmudar F Lasitschka M Etzrodt P Waterman MT Waring AT Chicoine AM van der Laan HW Niessen JJ Piek BB Rubin J Butany JR Stone HA Katus SA Murphy DA Morrow MS Sabatine C Vinegoni MA Moskowitz MJ Pittet P Libby CP Lin FK Swirski R Weissleder M Nahrendorf 《Nature》2012,487(7407):325-329
During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression. 相似文献