Future water quality monitoring - Adapting tools to deal with mixtures of pollutants in water resource management

Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects of anthropogenic chemical contamination from diffuse and point sources. While current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals can be detected simultaneously in our aquatic resources. However, exposure to chemical mixtures does not necessarily translate into adverse biological effects nor clearly shows whether mitigation measures are needed. Thus, the question which mixtures are present and which have associated combined effects becomes central for defining adequate monitoring and assessment strategies. Here we describe the vision of the international, EU-funded project SOLUTIONS, where three routes are explored to link the occurrence of chemical mixtures at specific sites to the assessment of adverse biological combination effects. First of all, multi-residue target and non-target screening techniques covering a broader range of anticipated chemicals co-occurring in the environment are being developed. By improving sensitivity and detection limits for known bioactive compounds of concern, new analytical chemistry data for multiple components can be obtained and used to characterise priority mixtures. This information on chemical occurrence will be used to predict mixture toxicity and to derive combined effect estimates suitable for advancing environmental quality standards. Secondly, bioanalytical tools will be explored to provide aggregate bioactivity measures integrating all components that produce common (adverse) outcomes even for mixtures of varying compositions. The ambition is to provide comprehensive arrays of effect-based tools and trait-based field observations that link multiple chemical exposures to various environmental protection goals more directly and to provide improved in situ observations for impact assessment of mixtures. Thirdly, effect-directed analysis (EDA) will be applied to identify major drivers of mixture toxicity. Refinements of EDA include the use of statistical approaches with monitoring information for guidance of experimental EDA studies. These three approaches will be explored using case studies at the Danube and Rhine river basins as well as rivers of the Iberian Peninsula. The synthesis of findings will be organised to provide guidance for future solution-oriented environmental monitoring and explore more systematic ways to assess mixture exposures and combination effects in future water quality monitoring.Seventh Framework Programme (E.U

Transfert de gène in vivo à l'aide de la polyéthylènimine (application à l'étude des cellules souches neurales)

The subventricular zone (SVZ) of the adult mammalian brain harbors the neural stem cell population with potential neural regeneration and repair capacity. We describe a nonviral technique to preferentially transfect in vivo the adult neural stem cell population and its immediate progeny based on intraventricular injection of polyethyelenimines (PEl)/DNA complexes. Linear PEI is proving to be efficient, non-toxic and versatile agent for in vivo gene delivery by a number of routes. The transfected population was identified by cellular and ultra-structural evidence showing their proliferating status and expression of the specific markers GFAP and nestin. Stable activation of the lacZ reporter by cre-recombinase transfection in R26R mice demonstrated survival and migration of stem cell derivatives three months after injection. Apoptosis is thought to be the most common fate of the stem cell progeny. Introduction of a neuroprotective, antiapoptotic gene Bcl-XL can augment the number and change the histological profile of transgene-expressing cells in the SVZ. This opens up the possibility of enhancing in situ the regenerative potential of this population of cells. As well as confirming the importance of apoptosis in neural stem cell physiology, our results pave the way for further investigations of this phenomenon. This method thus provides selective targeting of the stem cell population and should allow an in-depth understanding of their biology. We thus investigated the effects of thyroid hormones on proliferation and apoptosis of stem cells in the subventricular zone as well as on migration of transgene-tagged neuroblasts out of the stem cell niche. Hypothyroidism significantly reduced all three of these processes, inhibiting generation of new cells. These data suggest that, besides the well established multiple roles of TH in early neurogenesis, TH is an essential component of the endocrine environment that activates neural stem cell growth, migration, and apoptosis. Further, the results demonstrate that the negative effects of TH on mitotic capacity have repercussion on the number of cells migrating through the RMS. Endocrine factors such as TH could be key factors to reveal regenerative potential of endogenous or grafted stem cells.L'existence de cellules souches neurales dans le cerveau mammifère adulte revêt un vif intérêt aussi bien en recherche fondamentale que du point de vue des possibles applications thérapeutiques qu'elles pourraient représenter. Ainsi, il persiste dans la zone sub-ventriculaire (ZSV) des cellules capables de s'auto renouveler et de donner naissance à différents types cellulaires. Afin de comprendre la biologie de ces cellules, il est nécessaire de pouvoir les modifier génétiquement in vivo, au sein de la niche neurogénique où elles conservent leur nature souche. La polyethylènimine sous sa forme linéaire, est un polymère polycationique qui associe les avantages d'un vecteur synthétique de transfert de gène (faiblement toxique ou immunogène, souple d'utilisation, facile d'emploi...) à l'efficacité in vivo. Son utilisation dans le cerveau de souris nouveau-né ou adulte donne des niveaux importants d'expression du transgène. Une analyse plus précise par immuno-histochimie et microscopie éléctronique de la nature des cellules transfectées chez la souris adulte révèle que les complexes ADN/PEI ciblent préférentiellement les cellules souches neurales et les cellules progénitrices de la ZSV. L'introduction intraventriculaire de ces complexes permet de marquer génétiquement ces cellules et de suivre les précurseurs émergeant de la ZSV au cours de leur processus migratoire vers les bulbes olfactifs. De plus, nous démontrons qu'il est possible grâce à cette méthode modifier le devenir des cellules progénitrices de la ZSV. La surexpression du facteur anti-apoptotique Bcl-XL, permet de bloquer le phénomène d'apotose qui constitue le destin majeur des cellules issues de la niche neurogénique. Enfin, la possibilité d'introduire un matériel génétique de façon privilégiée dans cette population cellulaire peut être mise à profit pour suivre l'influence de l'état thyroïdien sur la biologie des cellules souches neurales. Il est ainsi démontré que l'hormone thyroïdienne est un élément endocrinien essentiel qui active la croissance cellulaire, la différenciation et l'apoptose des cellules souches neurales du cerveau mammifère adulte.PARIS-Museum Hist.Naturelle (751052304) / SudocSudocFranceF