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排序方式: 共有540条查询结果,搜索用时 15 毫秒
1.
  总被引:5,自引:0,他引:5  
Seven transmembrane receptors mediate diverse physiological responses including hormone action, olfaction, neurotransmission, and chemotaxis. Human D6 is a non-signaling seven-transmembrane receptor expressed on lymphatic endothelium interacting with most inflammatory CC-chemokines resulting in their rapid internalization. Here, we demonstrate that this scavenging activity is mediated by continuous internalization and constant surface expression of the receptor, a process involving the clathrin-coated pit-dependent pathway. D6 constitutively associates with the cytoplasmic adaptor beta-arrestin, and this interaction is essential for D6 internalization. An acidic region, but not the putative phosphorylation sites in the cytoplasmic tail of D6, is critical for receptor interaction with beta-arrestin and subsequent internalization. Neither the native D6 nor mutants uncoupled from beta-arrestin activate any G-protein-mediated signaling pathways. Therefore, D6 may be considered a decoy receptor structurally adapted to perform chemokine scavenging.  相似文献   
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Summary Expression of HLA-DR antigens by purified preparations of human ovarian carcinoma cells freshly isolated from surgical specimens was examined in parallel with the capacity of tumor cells to elicit a blastogenic response from autologous lymphocytes in mixed lymphocyte-tumor culture (MLTC) assay. Of 21 tumor preparations, 11 (52%) reacted with monoclonal antibodies 279 and/or 949 specific for a monomorphic determinant of HLA-DR antigens, with heterogeneous positivity, ranging between 30% and 95%. In this series of patients positive MLTC occurred in 8/21 individual experiments. The HLA-DR expression was proportionally similar in tumors giving positive MLTC (4/8=50%) and negative MLTC (7/13=53%). The lack of correlation between DR expression on tumor cells and stimulatory activity in autologous MLTC and the fact that DR-negative tumors could induce lymphocyte stimulation, support the hypothesis that blastogenesis occurs upon recognition of tumor-associated antigens, different from DR molecules, possibly tumor-specific antigens.  相似文献   
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The choice of an appropriate variant calling pipeline for exome sequencing data is becoming increasingly more important in translational medicine projects and clinical contexts. Within GOSgene, which facilitates genetic analysis as part of a joint effort of the University College London and the Great Ormond Street Hospital, we aimed to optimize a variant calling pipeline suitable for our clinical context. We implemented the GATK/Queue framework and evaluated the performance of its two callers: the classical UnifiedGenotyper and the new variant discovery tool HaplotypeCaller. We performed an experimental validation of the loss‐of‐function (LoF) variants called by the two methods using Sequenom technology. UnifiedGenotyper showed a total validation rate of 97.6% for LoF single‐nucleotide polymorphisms (SNPs) and 92.0% for insertions or deletions (INDELs), whereas HaplotypeCaller was 91.7% for SNPs and 55.9% for INDELs. We confirm that GATK/Queue is a reliable pipeline in translational medicine and clinical context. We conclude that in our working environment, UnifiedGenotyper is the caller of choice, being an accurate method, with a high validation rate of error‐prone calls like LoF variants. We finally highlight the importance of experimental validation, especially for INDELs, as part of a standard pipeline in clinical environments.  相似文献   
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Cell cycle regulation of NF-YC nuclear localization   总被引:3,自引:0,他引:3  
NF-Y is a trimeric activator with histone fold, HFM, subunits that binds to the CCAAT-box and is required for a majority of cell cycle promoters, often in conjunction with E2Fs. In vivo binding of NF-Y is dynamic during the cell cycle and correlates with gene activation. We performed immunofluorescence studies on endogenous, GFP- and Flag-tagged overexpressed NF-Y subunits. NF-YA, NF-YB are nuclear proteins. Unexpectedly, NF-YC localizes both in cytoplamatic and nuclear compartments and its nuclear localization is determined by the interaction with its heterodimerization partner NF-YB. Most importantly, compartmentalization is regulated during the cell cycle of serum restimulated NIH3T3 cells, accumulating in the nucleus at the onset of S phase. These data point to the control of HFM heterodimerization as an important layer of NF-Y regulation during cell cycle progression.  相似文献   
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This study examined the mechanisms underlying the intense activation of HIV-1-specific B cells observed in peripheral blood of HIV-1-infected subjects. Spontaneous in vitro synthesis of anti-HIV-1 antibodies, as well as total Ig production, were dramatically reduced by accessory cell, but not T cell removal. This fall was counteracted by addition of rIL-6, but not other cytokines, to monocyte-depleted cultures; moreover, antisera against IL-6 suppressed spontaneous anti-HIV-1 antibody synthesis in a dose-dependent manner. Although IL-6 apparently sustained HIV-1-specific B cell activation, no increase in serum IL-6 levels was observed; PBMC from seropositive subjects did not produce increased amounts of IL-6 in vitro, compared to seronegative controls, both spontaneously and in the presence of LPS stimulation; finally, no constitutive expression of IL-6 gene could be documented in freshly isolated PBMC. These findings indicate that IL-6 may play a central role in HIV-1-specific B cell activation in seropositive patients, and further stress the importance of this cytokine during HIV-1 infection.  相似文献   
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The occurrence of a trichinellosis epidemic in the province of Reggio Emilia in 1975, the source of which was attributed to horse meat, led the authors to use this animal for experimental infections. By using the trichina strain isolated from the above outbreak, 4 horses were infected orally. All 4 animals became infected. The most affected muscles were the lingual, masticatory and neck ones. Meat from the 4 horses was subsequently fed to laboratory animals (rats, mice, guineapigs) and other domestic species (cats, dogs, pigs) and further infections were obtained. An attempt to infect also a sheep was successful.  相似文献   
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