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991.
Castellino F Huang AY Altan-Bonnet G Stoll S Scheinecker C Germain RN 《Nature》2006,440(7086):890-895
CD8+ T cells have a crucial role in resistance to pathogens and can kill malignant cells; however, some critical functions of these lymphocytes depend on helper activity provided by a distinct population of CD4+ T cells. Cooperation between these lymphocyte subsets involves recognition of antigens co-presented by the same dendritic cell, but the frequencies of such antigen-bearing cells early in an infection and of the relevant naive T cells are both low. This suggests that an active mechanism facilitates the necessary cell-cell associations. Here we demonstrate that after immunization but before antigen recognition, naive CD8+ T cells in immunogen-draining lymph nodes upregulate the chemokine receptor CCR5, permitting these cells to be attracted to sites of antigen-specific dendritic cell-CD4+ T cell interaction where the cognate chemokines CCL3 and CCL4 (also known as MIP-1alpha and MIP-1beta) are produced. Interference with this actively guided recruitment markedly reduces the ability of CD4+ T cells to promote memory CD8+ T-cell generation, indicating that an orchestrated series of differentiation events drives nonrandom cell-cell interactions within lymph nodes, optimizing CD8+ T-cell immune responses involving the few antigen-specific precursors present in the naive repertoire. 相似文献
992.
Aharonian F Akhperjanian AG Bazer-Bachi AR Beilicke M Benbow W Berge D Bernlöhr K Boisson C Bolz O Borrel V Braun I Breitling F Brown AM Chadwick PM Chounet LM Cornils R Costamante L Degrange B Dickinson HJ Djannati-Ataï A Drury LO Dubus G Emmanoulopoulos D Espigat P Feinstein F Fontaine G Fuchs Y Funk S Gallant YA Giebels B Gillessen S Glicenstein JF Goret P Hadjichristidis C Hauser D Hauser M Heinzelmann G Henri G Hermann G Hinton JA Hofmann W Holleran M Horns D Jacholkowska A de Jager OC 《Nature》2006,439(7077):695-698
The source of Galactic cosmic rays (with energies up to 10(15) eV) remains unclear, although it is widely believed that they originate in the shock waves of expanding supernova remnants. At present the best way to investigate their acceleration and propagation is by observing the gamma-rays produced when cosmic rays interact with interstellar gas. Here we report observations of an extended region of very-high-energy (> 10(11) eV) gamma-ray emission correlated spatially with a complex of giant molecular clouds in the central 200 parsecs of the Milky Way. The hardness of the gamma-ray spectrum and the conditions in those molecular clouds indicate that the cosmic rays giving rise to the gamma-rays are likely to be protons and nuclei rather than electrons. The energy associated with the cosmic rays could have come from a single supernova explosion around 10(4) years ago. 相似文献
993.
994.
Deregulated expression of c-Myc depletes epidermal stem cells 总被引:30,自引:0,他引:30
The beta-catenin/TCF signaling pathway is essential for the maintenance of epithelial stem cells in the small intestine. c-Myc a downstream target of beta-catenin/TCF (ref. 2), can induce differentiation of epidermal stem cells in vitro. To determine the role of c-Myc in epidermal stem cells in vivo, we have targeted expression of human MYC2 to the hair follicles and the basal layer of mouse epidermis using a keratin 14 vector (K14.MYC2). Adult K14.MYC2 mice gradually lose their hair and develop spontaneous ulcerated lesions due to a severe impairment in wound healing; their keratinocytes show impaired migration in response to wounding. The expression of beta1 integrin, which is preferentially expressed in epidermal stem cells is unusually low in the epidermis of K14.MYC2 mice. Label-retaining analysis to identify epidermal stem cells reveals a 75% reduction in the number of stem cells in 3-month-old K14.MYC2 mice, compared with wildtype mice. We conclude that deregulated expression of c-Myc in stem cells reduces beta1 integrin expression, which is essential to both keratinocyte migration and stem cell maintenance. 相似文献
995.
996.
Ion conduction pore is conserved among potassium channels. 总被引:15,自引:0,他引:15
Potassium channels, a group of specialized membrane proteins, enable K+ ions to flow selectively across cell membranes. Transmembrane K+ currents underlie electrical signalling in neurons and other excitable cells. The atomic structure of a bacterial K+ channel pore has been solved by means of X-ray crystallography. To the extent that the prokaryotic pore is representative of other K+ channels, this landmark achievement has profound implications for our general understanding of K+ channels. But serious doubts have been raised concerning whether the prokaryotic K+ channel pore does actually represent those of eukaryotes. Here we have addressed this fundamental issue by substituting the prokaryotic pore into eukaryotic voltage-gated and inward-rectifier K+ channels. The resulting chimaeras retain the respective functional hallmarks of the eukaryotic channels, which indicates that the ion conduction pore is indeed conserved among K+ channels. 相似文献
997.
GPS定位和陀螺定向在大型贯通测量中的应用 总被引:1,自引:0,他引:1
详述了GPS定位和陀螺定向在大型贯通测量中的应用,并总结了煤矿测量的成功经验。 相似文献
998.
999.
Dopamine-beta-hydroxylase (DBH) activity was higher in the serum, the mesenteric artery and the cerebral cortex of 4-week-old stroke-prone spontaneously hypertensive rats (SHRSP), and lower in the nucleus tractus solitarii than it was in spontaneously hypertensive rats (SHR). 相似文献
1000.