Peripheral Blood Signatures of Lead Exposure

BACKGROUND: Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. METHODOLOGY/PRINCIPAL FINDING: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. CONCLUSIONS/SIGNIFICANCE: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway

Localism in Finland : The changing role and current crisis of the Finnish municipal system

Peer reviewe

Polyamine homeostasis:cellular responses to perturbation of polyamine biosynthetic enzymes

Abstract The polyamines putrescine, spermidine and spermine are highly regulated polycations present in virtually all cells of higher eukaryotes. They are essential for proper cell growth and differentiation by participating in various physiological processes including DNA, RNA and protein synthesis, apoptosis and interactions with ion-channels. The complexity of polyamine metabolism and the multitude of compensatory mechanisms that are invoked to maintain polyamine homeostasis argue that these molecules are critical for cell survival. The primary aim of this study was to gain a better understanding of the mode of action of polyamines and the regulatory mechanisms in which they are involved. Transgenic mice overexpressing the polyamine biosynthetic enzymes S-AdoMetDC and ODC were found to maintain their polyamine pools by acetylation of spermidine and spermine and an increased export of these acetylated compounds. The expression of various genes was studied as a response to polyamine deprivation in cell- and kidney organ culture. Among these genes acetyl-CoA synthetase and ornithine decarboxylase were demonstrated to be developmentally regulated. Changes in gene expression patterns, with most of the transcripts upregulated in the polyamine-depleted samples, indicated selective stabilization of mRNAs. Polyamines were shown to play an important role in kidney organogenesis as their depletion results in a reduction of ureteric branching and retardation of tubule formation. The selective changes of various genes in the ureteric bud and mesenchyme indicate that polyamines might have a role in the regulation of epithelial-mesenchymal interactions during mouse kidney development