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51.
Alley KE Cassady JM Fields H Glaser R Goodridge A Hoffsis GF Moser BD Sanfilippo F Yonushonis WP 《Science (New York, N.Y.)》2001,291(5512):2316-2317
52.
Partridge EA Le Roy C Di Guglielmo GM Pawling J Cheung P Granovsky M Nabi IR Wrana JL Dennis JW 《Science (New York, N.Y.)》2004,306(5693):120-124
The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up-regulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis. 相似文献
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Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4 总被引:1,自引:0,他引:1
Qureshi OS Zheng Y Nakamura K Attridge K Manzotti C Schmidt EM Baker J Jeffery LE Kaur S Briggs Z Hou TZ Futter CE Anderson G Walker LS Sansom DM 《Science (New York, N.Y.)》2011,332(6029):600-603
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system. 相似文献
54.
Corrine Noel Knapp Maria Fernandez-Gimenez Emily Kachergis Aleta Rudeen 《Strength and Conditioning Journal》2011,64(2):158-170
State-and-transition models (STMs) depict current understanding of vegetation dynamics and are being created for most ecological sites in the United States. Model creation is challenging due to inadequate long-term data, and most STMs rely on expert knowledge. There has been little systematic documentation of how different types of knowledge have been integrated in STMs, or what these distinct knowledge sources offer. We report on a series of participatory workshops where stakeholders helped to integrate STMs developed for the same region using local knowledge and ecological field data. With this exploratory project, we seek to understand what kinds of information local knowledge and ecological field data can provide to STMs, assess workshops as a method of integrating knowledge and evaluate how different stakeholders perceive models created with different types of knowledge. Our analysis is based on meeting notes, comments on draft models, and workshop evaluation questionnaires. We conclude that local knowledge and ecological data can complement one another, providing different types of information at different spatial and temporal scales. Participants reported that the workshop increased their knowledge of STMs and vegetation dynamics, suggesting that engaging potential model users in developing STMs is an effective outreach and education approach. Agency representatives and ranchers expressed the value of both the local knowledge and data-driven models. Agency participants were likely to critique or add components based on monitoring data or prior research, and ranchers were more likely to add states and transitions based on personal experience. As STM development continues, it is critical that range professionals think systematically about what different forms of data might contribute to model development, how we can best integrate existing knowledge and data to create credible and useful models, and how to validate the resulting STMs. 相似文献
55.
Matthias C. Rillig Emily R. Lutgen Philip W. Ramsey John N. Klironomos James E. Gannon 《Pedobiologia》2005,49(3):43
Arbuscular mycorrhizal fungi (AMF) are key components of ecosystems through their influence on plant communities and ecosystem processes. A major source of information regarding the importance of AMF species richness on process rates are mesocosm experiments using different levels of diversity of AMF as provided by single-species cultures of AMF. Since AMF inocula are generally made available in the form of non-sterile pot culture material, it is possible that AMF symbiosis-associated microbiota are at least partially responsible for some effects hitherto directly attributed to the AMF mycelium. Here, we provide evidence that microbiota associated with single-species cultures of AMF (after long-term pot culture enrichment of 7–8 years) can strongly affect the ecosystem process of soil aggregation. This effect occurred in an AMF isolate specific manner, but in the absence of live and active AMF mycelium. We additionally documented large differences in microbiota communities associated with the different AMF inocula (using PLFA analyses), suggesting that these differences were at least partly responsible for the observed changes in soil aggregation. This result points to AMF–microbiota interactions as a largely unexplored mechanism underlying soil aggregation (and potentially other ecosystem processes). We suggest that a reinterpretation of previous experiments using greenhouse-derived AMF cultures may be necessary, and the need to consider AMF symbiosis-associated microbiota in mechanistic studies of AMF and mycorrhizae in general is emphasized. 相似文献
56.
Michelle Casey Chris Gennings W. Hans Carter Virginia C. Moser Jane Ellen Simmons 《Journal of Agricultural, Biological & Environmental Statistics》2004,9(3):339-361
An important environmental and regulatory issue is the protection of human health from potential adverse effects of cumulative exposure to multiple chemicals. Earlier literature suggested restricting inference to specific fixed-ratio rays of interest. Based on appropriate definitions of additivity, single chemical data are used to predict the relationship among the chemicals under the zero-interaction case. Parametric comparisons between the additivity model and the model fit along the fixed-ratio ray(s) are used to detect departure from additivity. Collection of data along reduced fixed-ratio rays, where subsets of chemicals of interest are removed from the mixture and the remaining compounds are at the same relative ratios as considered in the full ray, allow researchers to make inference about the effect of the removed chemicals. Methods for fitting simultaneous confidence bands about the difference between the best fitting model and the model predicted under additivity are developed to identify regions along the rays where significant interactions occur. This general approach is termed the “single chemicals required” (SCR) method of analysis. A second approach, termed “single chemicals not required” (SCNR) method of analysis, is based on underlying assumptions about the parameterization of the response surface. Under general assumptions, polynomial terms for models fit along fixed-ratio rays are associated with interaction terms. Consideration is given to the case where only data along the mixture rays are available. Tests of hypotheses, which consider interactions due to subsets of chemicals, are also developed. 相似文献
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