This indicates, that as soon as an external stressor is sensed a fast response is favored, rather than the production of even higher colicin concentrations. In contrast, the average YFP fluorescence intensity per cell stays constant, and the colicin is released at earlier time-points at high exogenous stress levels. The intensity of the population wide response is then increased by a higher fraction of cells producing and releasing the colicin. In summary, we conclude that the level and kind of heterogeneity, in expression of the Colicin E2 operon, is adaptable to the environmental situation. Mast cells are distributed along both external and internal surfaces of the body. They are resident tissue cells that are frequently found in the connective tissue of the skin and around blood vessels and nerves. Mucosal MC, another subtype of MC, are also found in the mucosa of the airways and the intestine. Due to their tissue location MC are among the first cells to encounter bacteria, viruses and other foreign material that enter our tissues. These cells store a large amount of potent mediators in their cytoplasmic granules and the majority of the proteins found within these granules are serine proteases. These abundant granule proteases are stored in tight complexes with negatively charged proteoglycans and are released into the extracellular environment in response to immunological and neuronal stimuli. One subfamily of these proteases is the chymotrypsin-like chymases, which cleave at the C-terminal side of aromatic amino acids in substrates. Phylogenetic analyses of the KRX-0401 chymases have identified two distinct subfamilies, the achymases and the b-chymases. The a-chymases are found as a single gene in all species investigated, except for ruminants where two very similar a-chymase genes have been identified, whereas functional b-chymases have only been identified in rodents. We have previously determined the cleavage specificity from position P4 to P3�� in the human chymase. Besides the primary specificity for P1 Phe or Tyr, the strongest preference observed was for negatively charged aa residues in the P2�� position. Many natural XL-184 substrates for the HC also hold acidic aa residues in the P2�� position. These observations suggested an important role for negatively charged aa in the P2�� position during substrate discrimination by the HC. The structure of the HC has been extensively investigated, which has provided insight into important enzyme/substrate interactions. These studies have shown that Lys40, Arg143 and Lys192 are located close to the S2�� binding site, which may favour negatively charged P2�� side chains of substrates. In a recent report, we have tested the role of Arg143 and Lys192 as P2�� specificity determining residues.