Dichlorolissoclimide, a new cytotoxic labdane derivative from Lissoclinum voeltzkowi Michaelson (Urochordata)

Spectral methods were used to determine the structure of a new cytotoxic compound, dicnlorolissoclimide 1, isolated from the New Caledonian ascidian #Lissoclinum voeltzkowi$ Michaelson. (Résumé d'auteur

Three new potent cytotoxic macrolides closely related to sphinxolide from the New Caledonia sponge Neosiphonia superstes

Three new macrolides 2-4 have been isolated with sphinxolide 1 from the marine sponge #N. superstes$ collected off New Caledonia. The structures of the new compounds were determined by interpretation of NMR spectral data as well as comparison of spectral data with those of 1. These compounds were highly cytotoxic against various human carcinoma cells. (Résumé d'auteur

Random walks and polymers in the presence of quenched disorder

After a general introduction to the field, we describe some recent results concerning disorder effects on both `random walk models', where the random walk is a dynamical process generated by local transition rules, and on `polymer models', where each random walk trajectory representing the configuration of a polymer chain is associated to a global Boltzmann weight. For random walk models, we explain, on the specific examples of the Sinai model and of the trap model, how disorder induces anomalous diffusion, aging behaviours and Golosov localization, and how these properties can be understood via a strong disorder renormalization approach. For polymer models, we discuss the critical properties of various delocalization transitions involving random polymers. We first summarize some recent progresses in the general theory of random critical points : thermodynamic observables are not self-averaging at criticality whenever disorder is relevant, and this lack of self-averaging is directly related to the probability distribution of pseudo-critical temperatures $T_c(i,L)$ over the ensemble of samples $(i)$ of size $L$. We describe the results of this analysis for the bidimensional wetting and for the Poland-Scheraga model of DNA denaturation.Comment: 17 pages, Conference Proceedings "Mathematics and Physics", I.H.E.S., France, November 200

Automated workflow-based exploitation of pathway databases provides new insights into genetic associations of metabolite profiles

Background: Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) that associate with clinical phenotypes, but these SNPs usually explain just a small part of the heritability and have relatively modest effect sizes. In contrast, SNPs that associate with metabolite levels generally explain a higher percentage of the genetic variation and demonstrate larger effect sizes. Still, the discovery of SNPs associated with metabolite levels is challenging since testing all metabolites measured in typical metabolomics studies with all SNPs comes with a severe multiple testing penalty. We have developed an automated workflow approach that utilizes prior knowledge of biochemical pathways present in databases like KEGG and BioCyc to generate a smaller SNP set relevant to the metabolite. This paper explores the opportunities and challenges in the analysis of GWAS of metabolomic phenotypes and provides novel insights into the genetic basis of metabolic variation through the re-analysis of published GWAS datasets. Results: Re-analysis of the published GWAS dataset from Illig et al. (Nature Genetics, 2010) using a pathway-based workflow (http://www.myexperiment.org/packs/319.html), confirmed previously identified hits and identified a new locus of human metabolic individuality, associating Aldehyde dehydrogenase family1 L1 (ALDH1L1) with serine/glycine ratios in blood. Replication in an independent GWAS dataset of phospholipids (Demirkan et al., PLoS Genetics, 2012) identified two novel loci supported by additional literature evidence: GPAM (Glycerol-3 phosphate acyltransferase) and CBS (Cystathionine beta-synthase). In addition, the workflow approach provided novel insight into the affected pathways and relevance of some of these gene-metabolite pairs in disease development and progression. Conclusions: We demonstrate the utility of automated exploitation of background knowledge present in pathway databases for the analysis of GWAS datasets of metabolomic phenotypes. We report novel loci and potential biochemical mechanisms that contribute to our understanding of the genetic basis of metabolic variation and its relationship to disease development and progression

Varition in the flavonoid aglycone mixture excreted on the leaves of black alder (Alnus glutinosa) , from 12 different geographical origins

International audienc

Individual variation in the flavonoid aglycones excreted on the leaves of Alnus glutinosa : influence of culture conditions and origin of flavonoid natural diversity in wild specimens

International audienc