79 research outputs found

    Unmasking Chaotic Attributes in Time Series of Living Cell Populations

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    . Such complicated dynamics are generally the result of a combination of stochastic events and deterministic regulation. Assessing the role, if any, of chaotic regulation is difficult. However, unmasking chaotic dynamics is essential for analysis of cellular processes related to proliferation rate, including metabolic activity, telomere homeostasis, gene expression, and tumor growth.Using a simple, original, nonlinear method based on return maps, we previously found a geometrical deterministic structure coordinating such fluctuations in populations of various cell types. However, nonlinearity and determinism are only necessary conditions for chaos; they do not by themselves constitute a proof of chaotic dynamics. Therefore, we used the same analytical method to analyze the oscillations of four well-known, low-dimensional, chaotic oscillators, originally designed in diverse settings and all possibly well-adapted to model the fluctuations of cell populations: the Lorenz, Rössler, Verhulst and Duffing oscillators. All four systems also display this geometrical structure, coordinating the oscillations of one or two variables of the oscillator. No such structure could be observed in periodic or stochastic fluctuations.Theoretical models predict various cell population dynamics, from stable through periodically oscillating to a chaotic regime. Periodic and stochastic fluctuations were first described long ago in various mammalian cells, but by contrast, chaotic regulation had not previously been evidenced. The findings with our nonlinear geometrical approach are entirely consistent with the notion that fluctuations of cell populations can be chaotically controlled

    Docosapentaenoic acid (22:5n-3) down-regulates the expression of genes involved in fat synthesis in liver cells

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    Previous studies have shown that Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) exhibit triacylglycerol (TAG) lowering effect in vitro and in vivo by down-regulating the Sterol Regulating Element Binding Protein (SREBP-1c) and reducing the expression levels of lipogenic genes. However, there is no evidence on the effect of Docosapentaenoic Acid (DPA) on SREBP-1c expression levels. DPA is a long chain n-3 fatty acid present in our diet through fish, red meat and milk of ruminant animals. Therefore, this study aimed to elucidate the effect of DPA on liver fatty acid synthesis in an in vitro model using rat liver cells. Our results suggested that DPA incubation (50 μM) for 48 h (like EPA and DHA) caused a significant decrease in the mRNA expression levels of SREBP-1c, 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A reductase (HMG-CoA reductase), Acetyl Coenzyme A Carboxylase (ACC-1) and Fatty Acid Synthase (FASn) compared with Oleic Acid (OA) and also a decrease in the protein levels of SREBP-1 and ACC-1. A time-course fatty acid analysis showed that DPA and EPA are interconvertable in the cells; however, after 8 h of incubation with DPA, the cell phospholipids contained mainly DPA. The gene expression profiling of the lipogenic genes repeated at 8 h confirmed that the inhibitory effect of DPA on mRNA expression levels of the lipogenic genes was most likely due to DPA itself and not due to its conversion into EPA

    Deleted Chromosome 20 from a patient with Alagille syndrome isolated in a cell hybrid through leucine transport selection: study of three candidate genes

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    International audienceAlagille syndrome (AGS) is a well-defined ge-netic entity assigned to the short arm of Chromosome(Chr) 20 by a series of observations of AGS patients as-sociated with microdeletions in this region. By fusing lym-phoblastoid ceils of an AGS patient that exhibited a mi-crodeletion in the short arm of Chr 20 encompassing bandspl 1.23 to p12.3 with rodent thermosensitive mutant cells(CHOtsH 1-1) deficient in-leucyl-tRNA synthetase, we iso-lated a somatic cell hybrid segregating the deleted humanChr 20. This hybrid clone, designated NR2, was charac-terized by several methods, including PCR, with eightpairs of oligonucleotides mapped to Chr 20: D20S5,D20S41, D20S42, D20S56, D20S57, D20S58, adenosinedeaminase (ADA), and Prion protein (PRIP); RestrictionFragment Length Polymorphism (RFLP) analyses withfour genomic anonymous probes (D20S5, cD3H12,D20S 17, D20S 18); and fluorescent in situ hybridization(FISH) with total human DNA and D20Z1, a sequencespecific to the human Chr 20 centromere, as probes.The NR2 hybrid allowed us to exclude three candidategenes for AGS: hepatic nuclear factor 3 [3 (HNF3[3), pairedbox 1 (PAX1), and cystatin C (CST3) as shown by theirlocalization outside of the deletion. The NR2 hybrid is apowerful tool for the mapping of new probes of this region,as well as for obtaining new informative probes specific forthe deletion by subtractive cloning of the region. Suchmarkers will be useful for linkage analysis and screeningof cDNA libraries
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