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31.
Shi Y  Evans JE  Rock KL 《Nature》2003,425(6957):516-521
In infections, microbial components provide signals that alert the immune system to danger and promote the generation of immunity. In the absence of such signals, there is often no immune response or tolerance may develop. This has led to the concept that the immune system responds only to antigens perceived to be associated with a dangerous situation such as infection. Danger signals are thought to act by stimulating dendritic cells to mature so that they can present foreign antigens and stimulate T lymphocytes. Dying mammalian cells have also been found to release danger signals of unknown identity. Here we show that uric acid is a principal endogenous danger signal released from injured cells. Uric acid stimulates dendritic cell maturation and, when co-injected with antigen in vivo, significantly enhances the generation of responses from CD8+ T cells. Eliminating uric acid in vivo inhibits the immune response to antigens associated with injured cells, but not to antigens presented by activated dendritic cells. Our findings provide a molecular link between cell injury and immunity and have important implications for vaccines, autoimmunity and inflammation.  相似文献   
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Notch1 functions as a tumor suppressor in mouse skin   总被引:24,自引:0,他引:24  
Notch proteins are important in binary cell-fate decisions and inhibiting differentiation in many developmental systems, and aberrant Notch signaling is associated with tumorigenesis. The role of Notch signaling in mammalian skin is less well characterized and is mainly based on in vitro studies, which suggest that Notch signaling induces differentiation in mammalian skin. Conventional gene targeting is not applicable to establishing the role of Notch receptors or ligands in the skin because Notch1-/- embryos die during gestation. Therefore, we used a tissue-specific inducible gene-targeting approach to study the physiological role of the Notch1 receptor in the mouse epidermis and the corneal epithelium of adult mice. Unexpectedly, ablation of Notch1 results in epidermal and corneal hyperplasia followed by the development of skin tumors and facilitated chemical-induced skin carcinogenesis. Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors. Furthermore, Notch1 inactivation in the epidermis results in derepressed beta-catenin signaling in cells that should normally undergo differentiation. Enhanced beta-catenin signaling can be reversed by re-introduction of a dominant active form of the Notch1 receptor. This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin.  相似文献   
34.
Chemical analysis plays a significant role in the study of ancient ceramics[1,2]. Most ancient Chinese kilns used clays mined from the local areas and differences in the geochemistry and mineralogy of these raw materials may be expected. The chemical composition of ceramics may also be influenced by production techniques, such as processing by washing and mixing of different sorts of raw materials. These may also vary from kiln to kiln and even change over time. Thus the raw materials and pro…  相似文献   
35.
Two subspecies of Colorado chipmunk (state threatened and federal species of concern) occur in southern New MeXico: Tamias quadrivittatus australis in the Organ Mountains and T. q. oscuraensis in the Oscura Mountains. We developed a GIS model of potentially suitable habitat based on vegetation and elevation features, evaluated site classifications of the GIS model, and determined vegetation and terrain features associated with chipmunk occurrence. We compared GIS model classifications with actual vegetation and elevation features measured at 37 sites. At 60 sites we measured 18 habitat variables regarding slope, aspect, tree species, shrub species, and ground cover. We used logistic regression to analyze habitat variables associated with chipmunk presence/absence. All (100%) 37 sample sites (28 predicted suitable, 9 predicted unsuitable) were classified correctly by the GIS model regarding elevation and vegetation. For 28 sites predicted suitable by the GIS model, 18 sites (64%) appeared visually suitable based on habitat variables selected from logistic regression analyses, of which 10 sites (36%) were specifically predicted as suitable habitat via logistic regression. We detected chipmunks at 70% of sites deemed suitable via the logistic regression models. Shrub cover, tree density, plant proximity, presence of logs, and presence of rock outcrop were retained in the logistic model for the Oscura Mountains; litter, shrub cover, and grass cover were retained in the logistic model for the Organ Mountains. Evaluation of predictive models illustrates the need for multi-stage analyses to best judge performance. Microhabitat analyses indicate prospective needs for different management strategies between the subspecies. Sensitivities of each population of the Colorado chipmunk to natural and prescribed fire suggest that partial burnings of areas inhabited by Colorado chipmunks in southern New Mexico may be beneficial. These partial burnings may later help avoid a fire that could substantially reduce habitat of chipmunks over a mountain range.  相似文献   
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In October 1991 we recorded all black-tailed prairie dog ( Cynomys ludovicianus ) colonies and cattle points in a 1248-km 2 study area in southwest North Dakota and southeast Montana. Cattle point attractants were defined as fabricated water tanks and long-term supplemental feed sites. We found that a signivicant number of prairie dog colonies encompassed or adjoined cattle point attractants ( p < .001). Prairie dog colonies associated with cattle point attractants were a mean distance of 1.0 km from the next nearest town. The existence of cattle point attractants may encourage prairie dog colonization. Conversely, refraining from using long-term cattle point attractants can discourage prairie dog colonization.  相似文献   
38.
不同于传统数值计算方法,麦克斯韦电路(MC)理论融合了场的理论和路的理论,使二者高效地结合在一起.运用麦克斯韦电路理论分析方环散射体,研究方环散射体的MC求解方法以及MC的宽带特性,求出其散射电流,数值实验结果与矩量法结果吻合良好.研究还发现,MC可以在一个较宽的频带上得到准确电流解,因此,比其他数值方法更加高效和实用.  相似文献   
39.
The Least Bell&rsquo;s Vireo ( Vireo bellii pusillus ) was listed as state endangered in 1980 and federally endangered in 1986 in response to a sharp population decline and range reduction. This vireo commonly bred in riparian forests throughout the Central Valley of California, but prior to 2005, no nesting pairs had been confirmed in the region in over 50 years. On 29 June 2005, a Least Bell&rsquo;s Vireo nest was located in a 3-year-old riparian restoration site at the San Joaquin River National Wildlife Refuge in Stanislaus County, California. In 2006, a Least Bell&rsquo;s Vireo pair returned to the refuge to successfully breed, followed by an unsuccessful attempt in 2007 by an unpaired female. These records are approximately 350 km from the nearest known breeding population and appear to be part of a growing number of sightings outside of the species&rsquo; current southern California breeding range. These nesting attempts lend credence to the idea that extirpated species can recolonize restored habitat by long-distance dispersal.  相似文献   
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