Integrative biology : quantitative biosciences from nano to macro
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Paramecium cells swim and feed by beating their thousands of cilia in coordinated patterns. The organization of these patterns and its relationship with cell motility has been the subject of a large body of work, particularly as a model for ciliary beating in human organs where similar organization is seen. However the rapid motion of the cells makes quantitative measurements very challenging. ⋯ These measurements are repeated for four RNAi silenced mutants, where proteins specific to the cilia or to their connection to the cell base are depleted. We find that the mutants whose ciliary structure is affected display similar swimming to the control cells albeit with a reduced efficiency, while the mutations that affect the cilia's anchoring to the cell lead to strongly reduced ability to swim. This reduction in motility can be related to a loss of coordination between the ciliary beating in different parts of the cell.
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Mechanical ventilation has been a critical part of basic life support for many years, with almost one-third of all patients in the intensive care unit requiring the aid. However studies over the past two decades have indicated that ventilators have the potential to cause or aggravate pulmonary injury. The lung with its anatomically complex architecture and unique amalgam of cell types and interfaces is very difficult to replicate in vitro. ⋯ The prototype developed incorporates the ability to expose alveolar cells to sustained periods of supra-physiological pressure when cultured at an air-liquid interface with constant air-flow on the apical side and medium replenishment on basolateral surfaces. The in vitro evaluation of the alveolar, A549 and H441, cells indicated disruption of the cell layer integrity in response to sustained pressure application. The results indicate a magnitude- and duration-dependent response among both the cell types.
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A key role of the antioxidant glutathione is detoxification of chemically reactive electrophilic drug metabolites within the liver. Therefore glutathione depletion can have severe toxic consequences. Ophthalmic acid and 5-oxoproline are metabolites involved in glutathione metabolism, which can be measured readily in the blood and urine and have been proposed as candidate biomarkers of hepatic glutathione content. ⋯ Our model correctly predicted that hepatic glutathione depletion following paracetamol administration resulted in elevated concentrations of 5-oxoproline and ophthalmic acid in blood and of 5-oxoproline in urine. However, we also found from the model that concentrations of both of the compounds were likely to be influenced by prolonged administration of paracetamol and by the concentrations of intracellular metabolites such as methionine. We conclude that care must be taken when extrapolating from concentrations of these biomarkers to hepatic glutathione status.