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The term 'nutrient sensing' has been defined and interpreted in different ways. In the narrowest sense, a nutrient sensor is a protein whose binding to a nutrient leads to a change inthe function of that protein, which in some cases may triggerdownstream activation of a signalling cascade. Nutrients suchas AAs (amino acids), glucose and fatty acids have traditionallybeen considered as metabolic fuels for cell growthand development. But this view is undergoing a rapid changewith an increased understanding of the mechanisms bywhich such nutrients can act as mediators of signal transductionpathways. These nutrient-mediated signalling cascades regulate specific aspects of fuel and energy metabolism,ultimately influencing cell growth, proliferation and survival.
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Production of therapeutic recombinant proteins from mammalian systems is one of the fastest growing segments of the pharmaceutical market. Several analyses indicate that demand will eventually outpace production of these proteins. This imminent shortage has served to emphasize the need to improve on the yield that can be obtained from the systems currently in place. The majority of these proteins are produced in Chinese Hamster Ovary (CHO) cells, while the remainder are produced in a variety of other cell types including mouse myelomas NSO & SP2/0, baby hamster kidney (BHK) and a variety of others. CHO cells were first cultured in the late 1950's after their isolation from a chinese hamster (Cricetulus griseus) ovary epithelial tumor. Produced in CHO, tPA was the first of these recombinant proteins to receive approval for therapeutic use. Many changes to the process have occurred since that time, including changes to the cells, the growth medium and the reactor conditions to improve from that first venture. CHO remains the dominant force in biopharmaceutical production because it represents a cell line that is capable of incorporating the appropriate post-translational modifications, while at the same time maintaining the characteristics ideal for production culture.
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