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排序方式: 共有274条查询结果,搜索用时 31 毫秒
231.
Sally A. Nicholas Vladimir V. Bubnov Inna M. Yasinska Vadim V. Sumbayev 《Cellular and molecular life sciences : CMLS》2011,68(1):151-158
Inflammatory reactions to ssRNA viruses are induced by the endosomal Toll-like receptors (TLRs) 7 and 8. TLR7/8-mediated inflammatory
reaction results in activation of the Nalp3 inflammasome via an unknown mechanism. Here we report for the first time that
TLR7/8 mediate activation of xanthine oxidase (XOD) in an HIF-1α-dependent manner. XOD produces uric acid and reactive oxygen
species, which could activate Nalp3 and therefore induce activation of caspase 1, known to convert inactive pro-IL-1β into
active IL-1β. Specific inhibition of the XOD activity attenuates TLR7/8-mediated activation of caspase 1 and IL-1β release.
These results were obtained using human THP-1 myeloid macrophages. The findings were verified by conducting in vivo experiments
on mice. 相似文献
232.
Hillmer AM Brockschmidt FF Hanneken S Eigelshoven S Steffens M Flaquer A Herms S Becker T Kortüm AK Nyholt DR Zhao ZZ Montgomery GW Martin NG Mühleisen TW Alblas MA Moebus S Jöckel KH Bröcker-Preuss M Erbel R Reinartz R Betz RC Cichon S Propping P Baur MP Wienker TF Kruse R Nöthen MM 《Nature genetics》2008,40(11):1279-1281
We carried out a genome-wide association study in 296 individuals with male-pattern baldness (androgenetic alopecia) and 347 controls. We then investigated the 30 best SNPs in an independent replication sample and found highly significant association for five SNPs on chromosome 20p11 (rs2180439 combined P = 2.7 x 10(-15)). No interaction was detected with the X-chromosomal androgen receptor locus, suggesting that the 20p11 locus has a role in a yet-to-be-identified androgen-independent pathway. 相似文献
233.
Hunt KA Zhernakova A Turner G Heap GA Franke L Bruinenberg M Romanos J Dinesen LC Ryan AW Panesar D Gwilliam R Takeuchi F McLaren WM Holmes GK Howdle PD Walters JR Sanders DS Playford RJ Trynka G Mulder CJ Mearin ML Verbeek WH Trimble V Stevens FM O'Morain C Kennedy NP Kelleher D Pennington DJ Strachan DP McArdle WL Mein CA Wapenaar MC Deloukas P McGinnis R McManus R Wijmenga C van Heel DA 《Nature genetics》2008,40(4):395-402
Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways. 相似文献
234.
Morison IM Cramer Bordé EM Cheesman EJ Cheong PL Holyoake AJ Fichelson S Weeks RJ Lo A Davies SM Wilbanks SM Fagerlund RD Ludgate MW da Silva Tatley FM Coker MS Bockett NA Hughes G Pippig DA Smith MP Capron C Ledgerwood EC 《Nature genetics》2008,40(4):387-389
We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. Notably, the family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of most physiological apoptosis. 相似文献
235.
236.
Sarparanta J Jonson PH Golzio C Sandell S Luque H Screen M McDonald K Stajich JM Mahjneh I Vihola A Raheem O Penttilä S Lehtinen S Huovinen S Palmio J Tasca G Ricci E Hackman P Hauser M Katsanis N Udd B 《Nature genetics》2012,44(4):450-5, S1-2
Limb-girdle muscular dystrophy type 1D (LGMD1D) was linked to chromosome 7q36 over a decade ago, but its genetic cause has remained elusive. Here we studied nine LGMD-affected families from Finland, the United States and Italy and identified four dominant missense mutations leading to p.Phe93Leu or p.Phe89Ile changes in the ubiquitously expressed co-chaperone DNAJB6. Functional testing in vivo showed that the mutations have a dominant toxic effect mediated specifically by the cytoplasmic isoform of DNAJB6. In vitro studies demonstrated that the mutations increase the half-life of DNAJB6, extending this effect to the wild-type protein, and reduce its protective anti-aggregation effect. Further, we show that DNAJB6 interacts with members of the CASA complex, including the myofibrillar myopathy-causing protein BAG3. Our data identify the genetic cause of LGMD1D, suggest that its pathogenesis is mediated by defective chaperone function and highlight how mutations in a ubiquitously expressed gene can exert effects in a tissue-, isoform- and cellular compartment-specific manner. 相似文献
237.
Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes 总被引:1,自引:0,他引:1
Bonnefond A Clément N Fawcett K Yengo L Vaillant E Guillaume JL Dechaume A Payne F Roussel R Czernichow S Hercberg S Hadjadj S Balkau B Marre M Lantieri O Langenberg C Bouatia-Naji N;Meta-Analysis of Glucose Insulin-Related Traits Consortium 《Nature genetics》2012,44(3):297-301
Genome-wide association studies have revealed that common noncoding variants in MTNR1B (encoding melatonin receptor 1B, also known as MT(2)) increase type 2 diabetes (T2D) risk(1,2). Although the strongest association signal was highly significant (P < 1 × 10(-20)), its contribution to T2D risk was modest (odds ratio (OR) of ~1.10-1.15)(1-3). We performed large-scale exon resequencing in 7,632 Europeans, including 2,186 individuals with T2D, and identified 40 nonsynonymous variants, including 36 very rare variants (minor allele frequency (MAF) <0.1%), associated with T2D (OR = 3.31, 95% confidence interval (CI) = 1.78-6.18; P = 1.64 × 10(-4)). A four-tiered functional investigation of all 40 mutants revealed that 14 were non-functional and rare (MAF < 1%), and 4 were very rare with complete loss of melatonin binding and signaling capabilities. Among the very rare variants, the partial- or total-loss-of-function variants but not the neutral ones contributed to T2D (OR = 5.67, CI = 2.17-14.82; P = 4.09 × 10(-4)). Genotyping the four complete loss-of-function variants in 11,854 additional individuals revealed their association with T2D risk (8,153 individuals with T2D and 10,100 controls; OR = 3.88, CI = 1.49-10.07; P = 5.37 × 10(-3)). This study establishes a firm functional link between MTNR1B and T2D risk. 相似文献
238.
Bradfield JP Taal HR Timpson NJ Scherag A Lecoeur C Warrington NM Hypponen E Holst C Valcarcel B Thiering E Salem RM Schumacher FR Cousminer DL Sleiman PM Zhao J Berkowitz RI Vimaleswaran KS Jarick I Pennell CE Evans DM St Pourcain B Berry DJ Mook-Kanamori DO Hofman A Rivadeneira F Uitterlinden AG van Duijn CM van der Valk RJ de Jongste JC Postma DS Boomsma DI Gauderman WJ Hassanein MT Lindgren CM Mägi R Boreham CA Neville CE Moreno LA Elliott P Pouta A Hartikainen AL Li M Raitakari O 《Nature genetics》2012,44(5):526-531
Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1). 相似文献
239.
Yong Hu Samuel M.L.Teicher Brenden R.Ortiz Yang Luo Shuting Peng Linwei Huai Junzhang Ma Nicholas C.Plumb Stephen D.Wilson Junfeng He Ming Shi 《科学通报(英文版)》2022,(5):495-500
Exotic quantum phenomena may appear in material systems with multiple orders or phases,where the mutual interactions can give rise to new physics beyond that of... 相似文献
240.
Blaydon DC Ishii Y O'Toole EA Unsworth HC Teh MT Rüschendorf F Sinclair C Hopsu-Havu VK Tidman N Moss C Watson R de Berker D Wajid M Christiano AM Kelsell DP 《Nature genetics》2006,38(11):1245-1247
Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive conditions in which the only presenting phenotype is the absence or severe hypoplasia of all fingernails and toenails. After determining linkage to chromosome 20p13, we identified homozygous or compound heterozygous mutations in the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, in eight affected families. Rspo4 expression was specifically localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a crucial role in nail morphogenesis. 相似文献