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The evolution of hypermutators in response to antibiotic treatment in both clinical and laboratory settings provides a unique context for the study of adaptive evolution. With increased mutation rates, the number of hitchhiker mutations within an evolving hypermutator population is remarkably high and presents substantial challenges in determining which mutations are adaptive. Intriguingly however, hypermutators also provide an opportunity to explore deeply the accessible evolutionary trajectories that lead to increased organism fitness, in this case the evolution of antibiotic resistance to the clinically relevant antibiotic tigecycline by the hospital pathogen Acinetobacter baumannii. Using a continuous culture system, AB210M, a clinically derived strain of A. baumannii, was evolved to tigecycline resistance. Analysis of the adapted populations showed that nearly all the successful lineages became hypermutators via movement of a mobile element to inactivate mutS. In addition, metagenomic analysis of population samples revealed another 896 mutations that occurred at a frequency greater than 5% in the population, while 38 phenotypically distinct individual colonies harbored a total of 1712 mutations. These mutations were scattered throughout the genome and affected ~40% of the coding sequences. The most highly mutated gene was adeS, a known tigecycline-resistance gene; however, adeS was not solely responsible for the high level of TGC resistance. Sixteen other genes stood out as potentially relevant to increased resistance. The five most prominent candidate genes (adeS, rpsJ, rrf, msbA, and gna) consistently re-emerged in subsequent replicate population studies suggesting they are likely to play a role in adaptation to tigecycline. Interestingly, the repeated evolution of a hypermutator phenotype in response to antibiotic stress illustrates not only a highly adaptive strategy to resistance, but also a remarkably efficient survey of successful evolutionary trajectories.  相似文献   
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Summary If the aseptic plant material is regarded as a substrate for preservative microbial activity, it may be said that both the nitrogen and carbohydrate components undergo changes due to the influence of native enzymes in the plant material. These changes may very well be reflected in the microbial activity in a silage.It is interesting to compare the findings of this investigation, which show that during the days immediately after ensilage practically no changes take place when no bacteria are present. In a non-sterile ensilage, on the other hand, it is during this early stage that the briskest bacterial activity takes place.The chances of, say, an acid-forming microbial process actually lowering the pH in order that preservation of the material may take place are directly counteracted by the action of native enzymes of the vegetable material. During the days immediately after ensilage, however, if other conditions are favourable, microbial activity may clearly determine the whole course of events, and may possibly even inactivate the processes of the plant material itself.As is evident from the experiments described above, the activities inherent in the ensiled material itself are of no mean proportions. Further study of the mutual relationship of the ensilage and the various microbial fractions is therefore particularly necessary in order to be able to understand a number of processes of fundamental importance in biological preservation of plant material.  相似文献   
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Ohne Zusammenfassung  相似文献   
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Glucose oxidase (E.C 1.1.3.4) immobilized onto activated surface of mica was analyzed by enzymatic kinetics and visualization with atomic force microscopy (AFM). The activity of the immobilized enzyme decreased with the decrease of concentration of gamma-aminopropyltrimethoxysilane used for the first step of activation of mica, while AFM analysis showed similar homogeneous filling of the surface with the enzyme. The comparison of enzyme activity with its surface filling revealed that there has to be additional vertical structures, which cannot be visualized by the methods of AFM. The simultaneous decrease of the silanizing agent and the concentration of the enzyme led to molecular resolution for the enzyme on the surface of mica. This allows to propose the described method also for analyzing other surfaces of solid materials with coupled biomolecules.  相似文献   
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It is said that genetic modification (GM) of grain sorghum has the potential to alleviate hunger in Africa. To this end, millions of dollars have been committed to developing GM sorghum. Current developments in the genetic engineering of sorghum are similar to efforts to improve cassava and other traditional African crops, as well as rice in Asia. On closer analysis, GM sorghum is faced with the same limitations as 'Golden Rice' (GM rice) in the context of combating vitamin A deficiency (VAD) efficiently and sustainably. Thus, it is questionable whether the cost of developing GM sorghum can be justified when compared to the cost of investing in sustainable agricultural practice in Africa.  相似文献   
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