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排序方式: 共有71条查询结果,搜索用时 31 毫秒
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Ciaran P. Brady Richard L. Shimp Aaron P. Miles Michael Whitmore Anthony W. Stowers 《Protein expression and purification》2001,23(3):468-475
P30P2MSP1(19) is a recombinant subunit vaccine derived from merozoite surface protein 1 (MSP1) of Plasmodium falciparum, the causative agent of malaria. P30P2MSP1(19) consists of two universal T-cell epitopes fused to the most C-terminal 19-kDa portion of MSP1, and this protein has previously shown promising potential as a vaccine for malaria. However, previous attempts at producing this molecule in Saccharomyces cerevisiae resulted in the production of a truncated form of the molecule missing most of the universal T-cell epitopes. Here, we report the production of full-length P30P2MSP1(19) in Pichia pastoris. As salt precipitation is a common problem during P. pastoris high-density fermentation, we utilized an alternative low-salt, fully defined medium that did not reduce growth rates or biomass yields to avoid precipitation. A total of 500 mg/L of secreted purified protein was produced in high cell density fermentation and the protein was purified in one step utilizing nickel-chelate chromatography. P30P2MSP1(19) produced in Pichia was reactive with monoclonal antibodies that recognize only conformational epitopes on correctly folded MSP1. Rabbits immunized with this molecule generated higher and more uniform antibody titers than rabbits immunized with the protein produced in Saccharomyces. P30P2MSP1(19) produced in Pichia may prove to be a more efficacious vaccine than that produced in Saccharomyces and Pichia would provide a system for the cost-effective production of such a vaccine. 相似文献
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Shimp CP 《Behavioural processes》2001,54(1-3):11-32
Behavior analysis is examined from a social constructionist perspective. Constructionism is first defined and contrasted with a generic positivistic image of science. Behavior analysis, especially the matching law, is then viewed from both perspectives. The actual practice of behavior analysis (as opposed to the philosophy of radical behaviorism) more strongly resembles positivist than constructionist views. This alignment between behavior analysis and positivism emerges more sharply when positivist and constructionist perspectives are compared on the relation between science and music. Charles Rosen has identified how the classical style of musical composition and performance depended on 18th century keyboard technology, and a constructionist view sees the matching law as reflecting mid 20th century technology and culture in much the same way as it sees, say Mozart's 23rd piano concerto, as reflecting late 18th century culture. Behavior analysts, who often behave as though they see the matching law as an objective, impersonal, stable, hard, cold, incontrovertibly true fact, appear more inclined than constructionists to see a fundamental difference between the matching law and Mozart's 23rd piano concerto, to which they would attribute few if any of these characteristics. Possible implications are derived for tolerance in science. 相似文献
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Roepman P de Koning E van Leenen D de Weger RA Kummer JA Slootweg PJ Holstege FC 《Genome biology》2006,7(12):R117-12
Background
Metastasis, the process whereby cancer cells spread, is in part caused by an incompletely understood interplay between cancer cells and the surrounding stroma. Gene expression studies typically analyze samples containing tumor cells and stroma. Samples with less than 50% tumor cells are generally excluded, thereby reducing the number of patients that can benefit from clinically relevant signatures.Results
For a head-neck squamous cell carcinoma (HNSCC) primary tumor expression signature that predicts the presence of lymph node metastasis, we first show that reduced proportions of tumor cells results in decreased predictive accuracy. To determine the influence of stroma on the predictive signature and to investigate the interaction between tumor cells and the surrounding microenvironment, we used laser capture microdissection to divide the metastatic signature into six distinct components based on tumor versus stroma expression and on association with the metastatic phenotype. A strikingly skewed distribution of metastasis associated genes is revealed.Conclusion
Dissection of predictive signatures into different components has implications for design of expression signatures and for our understanding of the metastatic process. Compared to primary tumors that have not formed metastases, primary HNSCC tumors that have metastasized are characterized by predominant down-regulation of tumor cell specific genes and exclusive up-regulation of stromal cell specific genes. The skewed distribution agrees with poor signature performance on samples that contain less than 50% tumor cells. Methods for reducing tumor composition bias that lead to greater predictive accuracy and an increase in the types of samples that can be included are presented. 相似文献9.
The influence of readily degradable, naturally occurring carbon substrates on the biodegradation of several monosubstitued phenols (m-cresol, m-aminophenol, p-chlorophenol) was examined. The natural substrate classes used were amino acids, carbohydrates, and fatty acids. Samples of the microbial community from Lake Michie, a mesotrophic reservoir, were adapted to different levels of representatives from each natural substrate class in chemostats. After an extended adaptation period, the ability of the microbial community to degrade the monosubstituted phenols was determined by using a radiolabeled substrate uptake and mineralization method. Several microbiological characteristics of the communities were also measured. Adaptation to increasing concentrations of amino acids, carbohydrates, or fatty acids enhanced the ability of the microbial community to degrade all three phenols. The stimulation was largest for m-cresol and m-aminophenol. The mechanism responsible for the enhancement of monosubstituted phenol metabolism was not clearly identified, but the observation that adaptation to amino acids also increased the biodegradation of glucose and, to a lesser extent, naphthalene suggests a general stimulation of microbial metabolism. This study demonstrates that prior exposure to labile, natural substrates can significantly enhance the ability of aquatic microbial communities to respond to xenobiotics. 相似文献
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Nielsen J; Peixoto AA; Piccin A; Costa R; Kyriacou CP; Chalmers D 《Molecular biology and evolution》1994,11(6):839-853
The region of the clock gene period (per) that encodes a repetitive tract
of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran
species both within and outside the Drosophilidae. All the non-
Drosophilidae sequences in this region are short and present a remarkably
stable picture compared to the Drosophilidae, in which the region is much
larger and extremely variable, both in size and composition. The
accelerated evolution in the repetitive region of the Drosophilidae appears
to be mainly due to an expansion of two ancestral repeats, one encoding a
Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and
asparagine or threonine. In some drosophilids the expansion involves a
duplication of the pentapeptide sequence, but in Drosophila pseudoobscura
both the dipeptide and the pentapeptide repeats are present in larger
numbers. In the nondrosophilids, however, the pentapeptide sequence is
represented by one copy and the dipeptide by two copies. These observations
fulfill some of the predictions of recent theoretical models that have
simulated the evolution of repetitive sequences.
相似文献