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排序方式: 共有80条查询结果,搜索用时 15 毫秒
1.
Lamine Alaoui Gustavo Palomino Sandy Zurawski Gerard Zurawski Sixtine Coindre Nathalie Dereuddre-Bosquet Camille Lecuroux Cecile Goujard Bruno Vaslin Christine Bourgeois Pierre Roques Roger Le Grand Olivier Lambotte Benoit Favier 《Cellular and molecular life sciences : CMLS》2018,75(10):1871-1887
Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response. 相似文献
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A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma 总被引:1,自引:0,他引:1
Bertolotto C Lesueur F Giuliano S Strub T de Lichy M Bille K Dessen P d'Hayer B Mohamdi H Remenieras A Maubec E de la Fouchardière A Molinié V Vabres P Dalle S Poulalhon N Martin-Denavit T Thomas L Andry-Benzaquen P Dupin N Boitier F Rossi A Perrot JL Labeille B Robert C Escudier B Caron O Brugières L Saule S Gardie B Gad S Richard S Couturier J Teh BT Ghiorzo P Pastorino L Puig S Badenas C Olsson H Ingvar C Rouleau E Lidereau R Bahadoran P Vielh P Corda E Blanché H Zelenika D 《Nature》2011,480(7375):94-98
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Dina C Meyre D Gallina S Durand E Körner A Jacobson P Carlsson LM Kiess W Vatin V Lecoeur C Delplanque J Vaillant E Pattou F Ruiz J Weill J Levy-Marchal C Horber F Potoczna N Hercberg S Le Stunff C Bougnères P Kovacs P Marre M Balkau B Cauchi S Chèvre JC Froguel P 《Nature genetics》2007,39(6):724-726
We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses. 相似文献
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Holst F Stahl PR Ruiz C Hellwinkel O Jehan Z Wendland M Lebeau A Terracciano L Al-Kuraya K Jänicke F Sauter G Simon R 《Nature genetics》2007,39(5):655-660
Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers. Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification (P < 0.0001). In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification (P = 0.023). Notably, we also found ESR1 amplification in benign and precancerous breast diseases, suggesting that ESR1 amplification may be a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers. 相似文献
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Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
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Although previous research has considered habitat associations and breeding biology of Mountain Plovers in Wyoming at discrete sites, no study has considered these attributes at a statewide scale. We located 55 Mountain Plover nests in 6 counties across Wyoming during 2002 and 2003. Nests occurred in 2 general habitat types: grassland and desert-shrub. Mean estimated hatch date was 26 June ( n = 31) in 2002 and 21 June ( n = 24) in 2003. Mean hatch date was not related to latitude or elevation. Hatch success of nests was inferred in 2003 by the presence of eggshell fragments in the nest scrape. Eggs in 14 of 22 (64%) known-fate nests hatched. All grassland sites and 90% of desert sites were host to ungulate grazers, although prairie dogs were absent at 64% of nest sites. Nest plots had less grass coverage and reduced grass height compared with random plots. More than 50% of nests occurred on elevated plateaus. The Mountain Plover's tendency to nest on arid, elevated plateaus further substantiates claims that the bird is also a disturbed- prairie species. 相似文献
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A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors 总被引:1,自引:0,他引:1
Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signalling proteins, including HER-2/ErbB2, Akt, Raf-1, Bcr-Abl and mutated p53. Hsp90 inhibitors bind to Hsp90, and induce the proteasomal degradation of Hsp90 client proteins. Although Hsp90 is highly expressed in most cells, Hsp90 inhibitors selectively kill cancer cells compared to normal cells, and the Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is currently in phase I clinical trials. However, the molecular basis of the tumour selectivity of Hsp90 inhibitors is unknown. Here we report that Hsp90 derived from tumour cells has a 100-fold higher binding affinity for 17-AAG than does Hsp90 from normal cells. Tumour Hsp90 is present entirely in multi-chaperone complexes with high ATPase activity, whereas Hsp90 from normal tissues is in a latent, uncomplexed state. In vitro reconstitution of chaperone complexes with Hsp90 resulted in increased binding affinity to 17-AAG, and increased ATPase activity. These results suggest that tumour cells contain Hsp90 complexes in an activated, high-affinity conformation that facilitates malignant progression, and that may represent a unique target for cancer therapeutics. 相似文献
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