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Nathalie Ledirac

Publications and source records attributed to Nathalie Ledirac.

2 recordsLinked to original sources

Inferential, robust non-negative matrix factorization analysis of microarray data.

MOTIVATION: Modern methods such as microarrays, proteomics and metabolomics often produce datasets where there are many more predictor variables than observations. Research in these areas is often exploratory; even so, there is interest in statistical methods that accurately point to effects that are likely to replicate. Correlations among predictors are used to improve the statistical analysis. We exploit two ideas: non-negative matrix factorization methods that create ordered sets of predictors; and statistical testing within ordered sets which is done sequentially, removing the need for correction for multiple testing within the set. RESULTS: Simulations and theory point to increased statistical power. Computational algorithms are described in detail. The analysis and biological interpretation of a real dataset are given. In addition to the increased power, the benefit of our method is that the organized gene lists are likely to lead better understanding of the biology. AVAILABILITY: An SAS JMP executable script is available from http://www.niss.org/irMF

Algorithms↗

Effects of organochlorine insecticides on MAP kinase pathways in human HaCaT keratinocytes: key role of reactive oxygen species.

Organochlorine pesticides (OCs) are reported as potential carcinogens in humans. The aim of this study was to investigate the effects of four OCs (dieldrin, endosulfan, heptachlor, and lindane) on mitogen-activated protein kinase (MAPK) cascades and more specifically to identify the mechanism underlying OC-induced ERK1/2 activation. Organochlorine pesticides increased phosphorylated Raf, MEK1/2, ERK1/2, and c-Jun in human HaCaT cells, but they had no effect on p38 MAPK activation. Moreover, blockade of Raf, MEK1/2, or PKC activation with geldanamycin, U0126, or calphostin C inhibited ERK1/2 phosphorylation, demonstrating a PKC-Raf-MEK1/2 pathway. We also showed that these insecticides induced the production of reactive oxygen species (ROS). Pre-treatment with the antioxidant molecule N-acetyl cysteine sharply decreased the level of phospho-ERK1/2 and had no effect on Raf and MEK1/2 activation, suggesting a Raf-independent mechanism. This study indicates that OCs strongly activate the ERK1/2 pathway, and it identifies a critical role of ROS in OC-induced ERK activation, probably by stabilizing its phosphorylation.

Cell Line↗