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1.
Background
Eosinophilia plays the major role in the pathogenesis of asthma and correlates with the up‐regulation of eotaxin, which, together with interleukin (IL)‐5, is important for differentiation, chemo‐attraction, degranulation, and survival of eosinophils in local tissue. In a previous study, we found that administration of lentivirus‐delivered short hairpin RNA (shRNA) to suppress the expression of IL‐5 inhibited airway inflammation. The present study aimed to investigate the role of eotaxin shRNA and the synergistic effect of eotaxin and IL‐5 shRNAs on airway inflammation in an ovalbumin (OVA)‐induced murine model of asthma.Methods
Lentivirus‐delivered shRNAs were used to suppress the expression of eotaxin and/or IL‐5 in local tissue in an OVA‐induced murine asthma model.Results
Intra‐tracheal administration of lentivirus containing eotaxin shRNA expressing cassette (eoSEC3.3) efficiently moderated the characteristics of asthma, including airway hyper‐responsiveness, cellular infiltration of lung tissues, and eotaxin and IL‐5 levels in bronchio‐alveolar lavage fluid. Administration of lentiviruses expressing IL‐5 or eotaxin shRNAs (IL5SEC4 + eoSEC3.3) also moderated the symptoms of asthma in a mouse model.Conclusions
Local delivery of lentiviruses expressing IL‐5 and eotaxin shRNAs provides a potential tool in moderating airway inflammation and also has the potential for developing clinical therapy based on the application of shRNAs of chemokines and cytokines involved in T helper 2 cell inflammation and eosinophilia. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献2.
Summary The sensory receptor responsive to pressure applied internally to the ventral abdominal body wall of the blood-feeding insects, Rhodnius prolixus, is a single sense cell containing, at its distal end, a cilium enclosed within a scolopale, a densely staining structure characteristic of insect scolopidial sensilla. A small spherical structure lies within a dilation near the midregion of the cilium, and contains nine heavily staining bodies, the position of each corresponding to a pair of microtubules in the cilium. Proximal to the dilation, the microtubules are organized in a ring of nine pairs with one microtubule of each pair associated with dyneinlike arms. Dastal to the dilation a central pair of microtubules is present, but dyneinlike arms are absent. The scolopale cell, which gives risc to the scolopale, has cytoplasmic invaginations that form an elaborate array of extracellular compartments surrounding the body wall of the sense cell. These compartments may serve to dampen high frequency vibrations permitting the receptor to respond to pressure exerted by touch, an attribute in keeping with the receptor's proposed function of detecting abdominal distension related to the size and movement of the stomach. 相似文献
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4.
Ten different Polycomb group genes are required for spatial control of the abdA and AbdB homeotic products. 总被引:27,自引:0,他引:27
Mutations in genes of the Polycomb (Pc) group cause abnormal segmental development due to ectopic expression of the homeotic products of the Antennapedia and bithorax complexes. Here the requirements for Pc group genes in controlling the abdA and AbdB products of the bithorax complex are described. Embryos containing mutations in the genes Polycomb (Pc), extra sex combs (esc), Enhancer of zeste [E(z)], polyhomeotic (ph), Sex comb on midleg (Scm), Polycomb-like (Pcl), Sex comb extra (Sce), Additional sex combs (Asx), Posterior sex combs (Psc) and pleiohomeotic (pho) were examined. In every case, both abdA and AbdB are expressed outside of their normal domains along the anterior-posterior (A-P) axis, consistent with these Pc group products acting in a single pathway or molecular complex. The earliest detectable ectopic expression is highest in the parasegments immediately adjacent to the normal expression boundary. Surprisingly, in the most severe Pc group mutants, the earliest ectopic AbdB is distributed in a pair-rule pattern. At all stages, ectopic abdA in the epidermis is highest along the anterior edges of the parasegments, in a pattern that mimics the normal abdA cell-specific pattern. These examples of highly patterned mis-expression show that Pc group mutations do not cause indiscriminate activation of homeotic products. We suggest that the ectopic expression patterns result from factors that normally activate abdA and AbdB only in certain parasegments, but that in Pc group mutants these factors gain access to regulatory DNA in all parasegments. 相似文献
5.
Modulation of reconstituted cholesterol 7 alpha-hydroxylase by phosphatase and protein kinase 总被引:1,自引:0,他引:1
Cholesterol 7 alpha-hydroxylase activity was completely inhibited by incubation with alkaline phosphatase in a reconstituted enzyme system containing a cytochrome P-450, NADPH-cytochrome P-450 reductase and phospholipid. On the other hand, cAMP-dependent protein kinase stimulated cholesterol 7 alpha-hydroxylase activity by 2.5-fold. The modulation of cholesterol 7 alpha-hydroxylase activity was dependent on the amount of phosphatase or kinase added. The phosphatase inhibited enzyme activity was partially reversed by the treatment with protein kinase. These experiments indicate that the reconstituted cholesterol 7 alpha-hydroxylase activity is reversibly regulated by phosphorylation/dephosphorylation mechanism. 相似文献
6.
Transformation of Tobacco, Tomato, Potato, and Arabidopsis thaliana Using a Binary Ti Vector System 总被引:16,自引:1,他引:15
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Using a binary tumor-inducing (Ti) plasmid vector system, several plant species were transformed with a kanamycin resistance marker (neomycin phosphotransferase gene). Four Nicotiana species, seven tomato cultivars, two potato cultivars, and Arabidopsis thaliana were transformed by the binary vector transformation method. In this method, various plant organ pieces were co-cultivated with Agrobacterium tumefaciens cells carrying the binary vector, pGA472, and a helper Ti plasmid. We have also demonstrated that a wild type Ti plasmid can be used as a helper to obtain a transformed plant. 相似文献
7.
B淋巴细胞在多向造血祖细胞生长中的地位 总被引:3,自引:0,他引:3
小鼠骨髓细胞在体外培养中,加入用流式自由电泳法分离所得的高纯度正常B淋巴细胞,可使多向祖细胞(CFU-mix)集落增加至5倍;加入小鼠B淋巴瘤细胞株的条件培基(M_(12.4.1)-CM)时,CFU-mix数也可增加至4倍。单集落形态学分析结果表明M_(12.4.1)-CM可加强CFU-GEMm及p-BFU-E等早期造血祖细胞的增殖与分化。小鼠高纯度B细胞样品在体外培养中加入1000 rad照射的骨髓细胞可出现CFU-mix集落,如果再加入适量的小鼠肺条件培基,则CFU-mix数量比对照大15倍,其集落性质为CFU-GEMm,GMm及p-BFU-E。在此培养中加不同稀释度抗小鼠IgM血清,结果CFU-mix的产率与抗IgM血清的浓度成直线反比关系,当加入1:10抗小鼠IgM血清时,CFU-mix为0。作者假设在一定培养条件下,IgM阳性的部分B细胞可返祖转化为CFU-mix。 相似文献
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9.
Preparation and performance of immobilized yeast cells in columns containing no inert carrier 总被引:1,自引:0,他引:1
Schizosaccharomyces pombe was cultivated in a medium of glucose (10 g/L) malt extract (3 g/L), yeast extract (3 g/L), and bactopeptone (5 g/L) to form flocs. More than 95% of the cell population were flocculated. Variation in glucose concentration (from 10 to 100 g/L) did not affect flocculation. Yeast extract helped induce flocculation. Application of the immobilized yeast for the continuous production of ethanol was tested in a column reactor. Soft yeast flocs (50-200 mesh) underwent morphological changes to heavy particles (0.1-0.3 cm diameter) after continuously being fed with fresh substrates in the column. Productivity as high as 87 g EtOH L(-1) h(-1) was obtained when a 150 g/L glucose medium was fed. The performance of this yeast reactor was stable over a two-month period. The ethanol yield was 97% of the theoretical maximum based upon glucose consumed. 相似文献
10.
Equations were derived for the instantaneous relative sensitivities of reaction rates (controllability indices) and metabolite concentrations (response indices) to perturbations in the values of rate constants and were used to analyze the behavior of a model of in vivo glutamate metabolism in rat brain. Controllabilities of reversible reactions were found to increase as the values of the corresponding rate constants (i.e., the rate of approach to equilibrium) increased. Response indices generally declined with the metabolic distance between the metabolite and the rate constant, but they were unexpectedly high for reversible reactions with high controllabilities. The transient response of a given metabolite is most sensitive to reactions involving metabolites which are changing most rapidly relative to their respective pool sizes. Rapidly reversible reactions are most important for communication between metabolite pools. 相似文献