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101.
Winstone N Wilson AJ Morrow G Boggiano C Chiuchiolo MJ Lopez M Kemelman M Ginsberg AA Mullen K Coleman JW Wu CD Narpala S Ouellette I Dean HJ Lin F Sardesai NY Cassamasa H McBride D Felber BK Pavlakis GN Schultz A Hudgens MG King CR Zamb TJ Parks CL McDermott AB 《Journal of virology》2011,85(18):9578-9587
DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent "blips" in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication. 相似文献
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Dun Wang Xiao‐Fei Li Zheng‐Jian Zhou Xu‐Ping Feng Wan‐Jun Yang De‐An Jiang 《Physiologia plantarum》2010,139(1):55-67
Studies on some plant species have shown that increasing the growth temperature gradually or pretreating with high temperature can lead to obvious photosynthetic acclimation to high temperature. To test whether this acclimation arises from heat adaptation of ribulose 1,5‐bisphosphate carboxylase/oxygenase (Rubisco, EC 4.1.1.39) activation mediated by Rubisco activase (RCA), gene expression of RCA large isoform (RCAL) and RCA small isoform (RCAS) in rice was determined using a 4‐day heat stress treatment [40/30°C (day/night)] followed by a 3‐day recovery under control conditions [30/22°C (day/night)]. The heat stress significantly induced the expression of RCAL as determined by both mRNA and protein levels. Correlative analysis indicated that RCAS protein content was extremely significantly related to Rubisco initial activity and net photosynthetic rate (Pn) under both heat stress and normal conditions. Immunoblot analysis of the Rubisco–RCA complex revealed that the ratio of RCAL to Rubisco increased markedly in heat‐acclimated rice leaves. Furthermore, transgenic rice plants expressing enhanced amounts of RCAL exhibited higher thermotolerance in Pn and Rubisco initial activity and grew better at high temperature than wild‐type (WT) plants and transgenic rice plants expressing enhanced amounts of RCAS. Under normal conditions, the transgenic rice plants expressing enhanced amounts of RCAS showed higher Pn and produced more biomass than transgenic rice plants expressing enhanced amounts of RCAL and wild‐type plants. Together, these suggest that the heat‐induced RCAL may play an important role in photosynthetic acclimation to moderate heat stress in vivo, while RCAS plays a major role in maintaining Rubisco initial activity under normal conditions. 相似文献
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107.
Tianjiao Lyu Nan Jia Jieyu Wang Xiaohui Yan Yinhua Yu Zhen Lu Robert C Bast Jr Keqin Hua Weiwei Feng 《Epigenetics》2013,8(12):1330-1346
The initiation of angiogenesis can mark the transition from tumor dormancy to active growth and recurrence. Mechanisms that regulate recurrence in human cancers are poorly understood, in part because of the absence of relevant models. The induction of ARHI (DIRAS3) induces dormancy and autophagy in human ovarian cancer xenografts but produces autophagic cell death in culture. The addition of VEGF to cultures maintains the viability of dormant autophagic cancer cells, thereby permitting active growth when ARHI is downregulated, which mimics the “recurrence” of growth in xenografts. Two inducible ovarian cancer cell lines, SKOv3-ARHI and Hey-ARHI, were used. The expression level of angiogenesis factors was evaluated by real-time PCR, immunohistochemistry, immunocytochemistry and western blot; their epigenetic regulation was measured by bisulfite sequencing and chromatin immunoprecipitation. Six of the 15 angiogenesis factors were upregulated in dormant cancer cells (tissue inhibitor of metalloproteinases-3, TIMP3; thrombospondin-1, TSP1; angiopoietin-1; angiopoietin-2; angiopoietin-4; E-cadherin, CDH1). We found that TIMP3 and CDH1 expression was regulated epigenetically and was related inversely to the DNA methylation of their promoters in cell cultures and in xenografts. Increased H3K9 acetylation was associated with higher TIMP3 expression in dormant SKOv3-ARHI cells, while decreased H3K27me3 resulted in the upregulation of TIMP3 in dormant Hey-ARHI cells. Elevated CDH1 expression during dormancy was associated with an increase in both H3K4me3 and H3K9Ac in two cell lines. CpG demethylating agents and/or histone deacetylase inhibitors inhibited the re-growth of dormant cancer cells, which was associated with the re-expression of anti-angiogenic genes. The expression of the anti-angiogenic genes TIMP3 and CDH1 is elevated during dormancy and is reduced during the transition to active growth by changes in DNA methylation and histone modification. 相似文献
108.
Successful immune-mediated regression of solid tumors is difficult because of the small number of cytotoxic T lymphocytes (CTLs) that were traffic to the tumor site. Here, the targeting of tumor-specific infiltrating CTLs was dependent on a fusion protein consisting of human epidermal growth factor (EGF) and staphylococcal enterotoxin A (SEA) with the D227A mutation. EGF-SEA strongly restrained the growth of murine solid sarcoma 180 (S180) tumors (control versus EGF-SEA, mean tumor weight: 1.013 versus 0.197 g, difference = 0.816 g). In mice treated with EGF-SEA, CD4+, CD8+ and SEA-reactive T lymphocytes were enriched around the EGFR expressing tumor cells. The EGF receptors were potentially phosphorylated by EGF-SEA stimulation and the fusion protein promoted T cells to release the tumoricidal cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Intratumoral CTLs secreted cytolytic pore-forming perforins and granzyme B proteins near the surface of carcinomas, causing the death of many tumor cells. We additionally show that labeled EGF-SEA was directly targeted to the tumor tissue after intravenous (i.v.) injection. The findings demonstrate that antibody-like EGF-SEA plays an important role in arresting CTLs in the solid tumor site and has therapeutic potential as a tumor-targeting agent. 相似文献
109.
为防止呼吸机呼气管道中的含菌气体扩散污染病房空气,引发交叉感染。利用HEPA材料、活性炭、特殊的缓释杀菌滤材,研制成一套呼吸机呼气除菌过滤装置。经参照有关标准用物理模拟气溶胶颗粒(0.28-0.34um)及微生物气溶胶测试,过滤效率>99.995%,微生物气溶胶滤除率达100%。气流阻力<230Pa,完全能满足临床呼气机的过滤除菌使用条件。 相似文献
110.
Synergistic interactions between Glomus mosseae and Bradyrhizobium japonicum in enhancing proton release from nodules and hyphae 总被引:1,自引:0,他引:1
Soybean (Glycine max L. Merr.) seedlings were inoculated with Glomus mosseae (GM) and Bradyrhizobium japonicum (BJ) together or separately to study the effect of interactions on net H+ effluxes of nodules or extraradical hyphae by in vivo vibrating electrode techniques. GM promoted three-fold the H+ effluxes of nodules on mycorrhizal lateral roots and BJ increased eight-fold the net H+ effluxes of hyphae developing in the vicinity of nodules on lateral roots. Increments in plant P content were positively
and linearly correlated with the net H+ efflux of nodules and hyphae. It is concluded that increased H+ effluxes of nodules resulted from enhanced nitrogenase activities induced by the presence of the AM fungus in lateral roots.
The results point to additive effects of interactions between mycorrhizal fungi and rhizobia in increasing the extent of acidification
of the “nodulesphere” and the hyposphere. 相似文献