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排序方式: 共有209条查询结果,搜索用时 125 毫秒
91.
Phylogeography and evolutionary history of reassortant H9N2 viruses with potential human health implications 总被引:2,自引:0,他引:2
Fusaro A Monne I Salviato A Valastro V Schivo A Amarin NM Gonzalez C Ismail MM Al-Ankari AR Al-Blowi MH Khan OA Maken Ali AS Hedayati A Garcia Garcia J Ziay GM Shoushtari A Al Qahtani KN Capua I Holmes EC Cattoli G 《Journal of virology》2011,85(16):8413-8421
Avian influenza viruses of the H9N2 subtype have seriously affected the poultry industry of the Far and Middle East since the mid-1990s and are considered one of the most likely candidates to cause a new influenza pandemic in humans. To understand the genesis and epidemiology of these viruses, we investigated the spatial and evolutionary dynamics of complete genome sequences of H9N2 viruses circulating in nine Middle Eastern and Central Asian countries from 1998 to 2010. We identified four distinct and cocirculating groups (A, B, C, and D), each of which has undergone widespread inter- and intrasubtype reassortments, leading to the generation of viruses with unknown biological properties. Our analysis also suggested that eastern Asia served as the major source for H9N2 gene segments in the Middle East and Central Asia and that in this geographic region within-country evolution played a more important role in shaping viral genetic diversity than migration between countries. The genetic variability identified among the H9N2 viruses was associated with specific amino acid substitutions that are believed to result in increased transmissibility in mammals, as well as resistance to antiviral drugs. Our study highlights the need to constantly monitor the evolution of H9N2 viruses in poultry to better understand the potential risk to human health posed by these viruses. 相似文献
92.
Recognition and killing of human and murine pancreatic beta cells by the NK receptor NKp46 总被引:1,自引:0,他引:1
Gur C Enk J Kassem SA Suissa Y Magenheim J Stolovich-Rain M Nir T Achdout H Glaser B Shapiro J Naparstek Y Porgador A Dor Y Mandelboim O 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(6):3096-3103
Type 1 diabetes is an incurable disease that is currently treated by insulin injections or in rare cases by islet transplantation. We have recently shown that NKp46, a major killer receptor expressed by NK cells, recognizes an unknown ligand expressed by β cells and that in the absence of NKp46, or when its activity is blocked, diabetes development is inhibited. In this study, we investigate whether NKp46 is involved in the killing of human β cells that are intended to be used for transplantation, and we also thoroughly characterize the interaction between NKp46 and its human and mouse β cell ligands. We show that human β cells express an unknown ligand for NKp46 and are killed in an NKp46-dependent manner. We further demonstrate that the expression of the NKp46 ligand is detected on human β cells already at the embryonic stage and that it appears on murine β cells only following birth. Because the NKp46 ligand is detected on healthy β cells, we wondered why type 1 diabetes does not develop in all individuals and show that NK cells are absent from the vicinity of islets of healthy mice and are detected in situ in proximity with β cells in NOD mice. We also investigate the molecular mechanisms controlling NKp46 interactions with its β cell ligand and demonstrate that the recognition is confined to the membrane proximal domain and stalk region of NKp46 and that two glycosylated residues of NKp46, Thr(125) and Asn(216), are critical for this recognition. 相似文献
93.
Cissé M Duplan E Guillot-Sestier MV Rumigny J Bauer C Pagès G Orzechowski HD Slack BE Checler F Vincent B 《The Journal of biological chemistry》2011,286(33):29192-29206
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95.
D'Arcy P Brnjic S Olofsson MH Fryknäs M Lindsten K De Cesare M Perego P Sadeghi B Hassan M Larsson R Linder S 《Nature medicine》2011,17(12):1636-1640
Ubiquitin-tagged substrates are degraded by the 26S proteasome, which is a multisubunit complex comprising a proteolytic 20S core particle capped by 19S regulatory particles. The approval of bortezomib for the treatment of multiple myeloma validated the 20S core particle as an anticancer drug target. Here we describe the small molecule b-AP15 as a previously unidentified class of proteasome inhibitor that abrogates the deubiquitinating activity of the 19S regulatory particle. b-AP15 inhibited the activity of two 19S regulatory-particle-associated deubiquitinases, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b-AP15 induced tumor cell apoptosis that was insensitive to TP53 status and overexpression of the apoptosis inhibitor BCL2. We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target. 相似文献
96.
Meurs L Labuda L Amoah AS Mbow M Ngoa UA Boakye DA Mboup S Dièye TN Mountford AP Turner JD Kremsner PG Polman K Yazdanbakhsh M Adegnika AA 《PloS one》2011,6(9):e24393
Background
Schistosoma infection is thought to lead to down-regulation of the host''s immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands.Methodology
Peripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zilé in Gabon. PBMCs were incubated for 24 h and 72 h with various TLR ligands, as well as schistosomal egg antigen (SEA) and adult worm antigen (AWA). Pro-inflammatory TNF-α and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants.Principal Findings
Infected children produced higher adaptive IL-10 responses than uninfected children against schistosomal antigens (72 h incubation). On the other hand, infected children had higher TNF-α responses than uninfected children and significantly higher TNF-α to IL-10 ratios in response to FSL-1 and Pam3, ligands of TLR2/6 and TLR2/1 respectively. A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation).Conclusions
This pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response. This suggests that S. haematobium infection does not suppress the host''s innate immune system in the context of single TLR ligation. 相似文献97.
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Anne-Christine Bay-Jensen Nadine CB Tabassi Lene V Sondergaard Thomas L Andersen Frederik Dagnaes-Hansen Patrick Garnero Moustapha Kassem Jean-Marie Delaissé 《Arthritis research & therapy》2009,11(1):R9