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The currently used regulatory in vitro mutagenicity/genotoxicity test battery has a high sensitivity for detecting genotoxicants, but it suffers from a large number of irrelevant positive results (i.e. low specificity) thereby imposing the need for additional follow-up by in vitro and/or in vivo genotoxicity tests. This could have a major impact on the cosmetic industry in Europe, seen the imposed animal testing and marketing bans on cosmetics and their ingredients. Afflicted, but safe substances could therefore be lost. Using the example of triclosan, a cosmetic preservative, we describe here the potential applicability of a human toxicogenomics-based in vitro assay as a potential mechanistically based follow-up test for positive in vitro genotoxicity results. Triclosan shows a positive in vitro chromosomal aberration test, but is negative during in vivo follow-up tests. Toxicogenomics analysis unequivocally shows that triclosan is identified as a compound acting through non-DNA reactive mechanisms. This proof-of-principle study illustrates the potential of genome-wide transcriptomics data in combination with in vitro experimentation as a possible weight-of-evidence follow-up approach for de-risking a positive outcome in a standard mutagenicity/genotoxicity battery. As such a substantial number of cosmetic compounds wrongly identified as genotoxicants could be saved for the future., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to verify whether male patients with psychosis have greater neurocognitive impairment than female patients at illness onset., Method: Participants with a first episode of psychosis (74 women/86 men) and healthy controls (62 women/97 men) were assessed with an extensive neuropsychological test battery., Results: Women in the clinical group were older at illness onset and had achieved higher formal education than men. This trend was the same for the control group. The patient group presented with lower premorbid IQ compared to healthy controls, and performed below for most neuropsychological tests. Women scored higher than men on a test of verbal memory, whereas men scored higher than women on a test of reaction time, visual memory, and a planning task. There were no group-by-sex interactions for any of the neuropsychological tests., Conclusion: The present study shows that at the onset of psychosis there are no differences between males and females in neuropsychological performance. The differential pattern of cognitive performance observed is similar to that in healthy males and females. Furthermore, females with a late onset of psychosis may represent a subgroup with specific visuospatial and problem solving impairments., (© 2013.)

A strict control of abundance and localization of plasma membrane proteins is essential for plants to be able to respond quickly and accurately to a changing environment. The proteins responsible for the initial recognition and concentration of ubiquitinated plasma membrane proteins destined for degradation, are well characterized in mammals and yeast, (1) yet no clear orthologs were found in plants. (2) Recently, we have identified a family of proteins in higher plants, which function in vacuolar targeting and subsequent degradation of ubiquitinated plasma membrane proteins (3,4) termed TOM1-like (TOL) proteins.

Ethnopharmacological Relevance: Traditional Mongolian medicine (TMM) uses preparations from herbs as one form of medication for the treatment of a diversity of diseases including diabetes mellitus (DM). We evaluated the effect of extracts from the plant Leonurus sibiricus L. (LS), used in TMM to treat typical symptoms of type 2 DM, on insulin secretion, electrophysiological properties, intracellular calcium concentration and cell proliferation of INS-1E insulinoma cells under standard cell culture conditions (SCC; 11.1mM glucose)., Materials and Methods: Insulin secretion was measured by ELISA, electrical properties were assessed by whole cell patch clamping, intracellular calcium concentration (Cai) by Fluo-4 time lapse imaging, insulin receptor expression was verified by RT-PCR and cell proliferation assessed by CellTiter-Glo® cell viability assay., Results: Insulin released from INS-1E cells into the culture medium over 24h was significantly increased in presence of 500 mg/L aqueous LS extract (LS OWE) as well as methanolic LS extract (LS MeOH/H2O) but not in the presence of the butanol-soluble extract (LS MeOH/BuOH). Acute application of LS OWE resulted in a depolarization of the cell membrane potential paralleled by an initial increase and subsequent decline and silencing of action potential frequency, by KATP channel inhibition, persisting depolarization and an increase in Cai. The electrophysiological effects were comparable to those of 100 μM tolbutamide, which, however failed to elevate insulin secretion under SCC. Furthermore all LS extracts stimulated INS-1E cell proliferation., Conclusions: The finding that extracts from Leonurus sibiricus L. enhance insulin secretion and/or foster cell proliferation may provide possible explanations for the underlying therapeutic principles in the empirical use of LS-containing formulations in DM and DM-related disorders as applied in TMM., (© 2013 Elsevier Ireland Ltd. All rights reserved.)