Human mucin genes MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 express stable and extremely large mRNAs and exhibit a variable length polymorphism. An improved method to analyze large mRNAs.

Of the nine mucin genes that have been characterized, only MUC1 and MUC7 have been fully sequenced, and their transcripts can be detected as distinct bands of predicted size by Northern blot analysis. In contrast, the RNA patterns observed for each of the other MUC genes have usually shown a very high degree of polydispersity. This polydispersity has been believed to be one of the typical features of the mucin mRNAs, but until now, its origin has remained unexplained. In the work described in the present paper, we investigated two possible kinds of explanation for this phenomenon: namely that the extensive polydispersity results from a biological mechanism or that it is artifactual in origin. The data obtained, as a result of improving the purification and blotting methods, allowed us to show that in all of the tissues analyzed, each of the genes, MUC2-6, expresses mRNAs that are stable and are of an unusually large size to be found in eukaryotes (14-24 kilobases). Moreover, allelic variations in length of these mucin transcripts were observed. We demonstrate that these variations are directly related to the variable number of tandem repeat polymorphisms seen at the DNA level.

Uptake and biological transformation of beta NiS and alpha Ni3S2 by human embryonic pulmonary epithelial cells (L132) in culture.

The cytotoxicity, biological transformation and interaction with plasma membranes of alpha Ni3S2 and beta NiS were studied on human embryonic pulmonary epithelial cells (L132 cell line) in culture. By establishing growth curves and survival curves, it was found that at equal molarity beta NiS has a higher inhibitory effect on cell growth than alpha Ni3S2 but a lower cytotoxic effect: the CL50 being 60 and 40 mumols/l respectively. As to their uptake, beta NiS crystals are preferentially phagocytized in their original form and then probably dissolved in the vacuoles, whereas alpha Ni3S2 is transformed in the extracellular space and in the phagocytic vacuoles into minute particles (10 nm) that are recovered bound to the cell membrane, phagocytic vacuoles and lysosomal membranes respectively. Energy dispersive spectrometry revealed that the particles bound to cell membranes no longer contain sulfur but only phosphorus and nickel as inorganic compounds. This observation suggests the formation of a Ni/P complex with the phosphate groups of membranous phospholipids and/or phosphotransferring proteins. The steady-state fluorescence polarization analysis, however, revealed a significant increase of membrane fluidity either induced by desaturation of aliphatic chains or directly by the cleavage of the fatty acid chains. These results clearly show a difference between beta NiS and alpha Ni3S2 concerning their cytotoxic effects, uptake, biological transformation and interaction with cell membranes.

Additive models for dependent cell populations.

We propose an additive model for cell population growth which allows for positive correlation between sister cell lifetimes but arbitrary correlations between mother and daughter cell lifetimes. In the model each cell lifetime is the sum of two independent components, one of which is shared with its sister cell and which is also a function of the components of the lifetime of their mother. Assuming that the components follow a gamma distribution, the model is fitted to cell lifetime data of EMT6 cells obtained by the method of time-lapse cinematography.