Non Ribosomal Peptides : A monomeric puzzle

National audienceNonribosomal peptides (NRPs) are increasingly studied because they harbor activities which can be exploited in various domains. They are often denoted as graphs illustrating their chemical structure, where the atoms are represented by nodes and the chemical bonds by arcs. Another possible representation is the monomeric structure. This structure, inspired by the biosynthetic pathway of these peptides, is effectuated by large enzymatic complexes which assemble together smaller compounds called monomers. Consequently, the nonribosomal peptides are composed of a great variety of monomers (more than 500 are known) including amino acids, lipids and carbohydrates. Likewise, nonpetidic bonds are formed between multiple monomers, producing peptides with cycles and/or branches. Thus, the monomeric structure is a graph formed by the monomers present in the peptide and their interlinking chemical bonds. Until now, there did not exist a tool allowing for the conversion between the atomic and monomeric structures. This article presents a novel algorithm capable of localising the monomers from a reference list in the chemical structures of peptides extracted from the Norine database. The algorithm is based on a heuristic that utilizes chemical information of NRPs. The preliminary results are encouraging, and should lead to further studies.Les peptides non-ribosomiques (NRP) sont des molécules de plus en plus étudiées car elles présentent des activités ayant des applications principalement dans le domaine pharmaceutique. Elles sont souvent décrites par leur structure chimique, c'est-a-dire un graphe dont les noeuds sont des atomes et les arêtes les liaisons chimiques. Une autre représentation possible est la structure monomérique. Cette structure, inspirée de la voie de synthèse de ces peptides, est réalisé par de gros complexes enzymatiques qui assemblent les briques de base, appelées monomères. Ainsi, les peptides non-ribosomiques sont composés d'une grande variété de monomères (plus de 500 recensés jusqu'à présent) tels que des acides aminés, mais aussi des lipides ou des sucres. De plus, des liaisons non-peptidiques peuvent être formées entre certains monomères, ce qui produit des peptides contenant des cycles et/ou des branchements. La structure monomérique est donc le graphe formé par les monomères présents dans le peptide et les liaisons qui les relient. A l'heure actuelle, il n'existe pas d'outil permettant de convertir la structure chimique d'un peptide non-ribosomique en sa structure monomérique. Cet article présente un algorithme capable de localiser les monomères d'une liste de référence dans les structures chimiques des peptides de la base de données Norine. Il est basé sur une heuristique gloutonne qui utilise des connaissances sur la chimie des NRP. Les résultats préliminaires sont satisfaisants et devraient conduire à de nouvelles études

Non Ribosomal Peptides : A monomeric puzzle

National audienceNonribosomal peptides (NRPs) are increasingly studied because they harbor activities which can be exploited in various domains. They are often denoted as graphs illustrating their chemical structure, where the atoms are represented by nodes and the chemical bonds by arcs. Another possible representation is the monomeric structure. This structure, inspired by the biosynthetic pathway of these peptides, is effectuated by large enzymatic complexes which assemble together smaller compounds called monomers. Consequently, the nonribosomal peptides are composed of a great variety of monomers (more than 500 are known) including amino acids, lipids and carbohydrates. Likewise, nonpetidic bonds are formed between multiple monomers, producing peptides with cycles and/or branches. Thus, the monomeric structure is a graph formed by the monomers present in the peptide and their interlinking chemical bonds. Until now, there did not exist a tool allowing for the conversion between the atomic and monomeric structures. This article presents a novel algorithm capable of localising the monomers from a reference list in the chemical structures of peptides extracted from the Norine database. The algorithm is based on a heuristic that utilizes chemical information of NRPs. The preliminary results are encouraging, and should lead to further studies.Les peptides non-ribosomiques (NRP) sont des molécules de plus en plus étudiées car elles présentent des activités ayant des applications principalement dans le domaine pharmaceutique. Elles sont souvent décrites par leur structure chimique, c'est-a-dire un graphe dont les noeuds sont des atomes et les arêtes les liaisons chimiques. Une autre représentation possible est la structure monomérique. Cette structure, inspirée de la voie de synthèse de ces peptides, est réalisé par de gros complexes enzymatiques qui assemblent les briques de base, appelées monomères. Ainsi, les peptides non-ribosomiques sont composés d'une grande variété de monomères (plus de 500 recensés jusqu'à présent) tels que des acides aminés, mais aussi des lipides ou des sucres. De plus, des liaisons non-peptidiques peuvent être formées entre certains monomères, ce qui produit des peptides contenant des cycles et/ou des branchements. La structure monomérique est donc le graphe formé par les monomères présents dans le peptide et les liaisons qui les relient. A l'heure actuelle, il n'existe pas d'outil permettant de convertir la structure chimique d'un peptide non-ribosomique en sa structure monomérique. Cet article présente un algorithme capable de localiser les monomères d'une liste de référence dans les structures chimiques des peptides de la base de données Norine. Il est basé sur une heuristique gloutonne qui utilise des connaissances sur la chimie des NRP. Les résultats préliminaires sont satisfaisants et devraient conduire à de nouvelles études

An improved whole life cycle culture protocol for the hydrozoan genetic model Clytia hemisphaerica

The jellyfish species Clytia hemisphaerica (Cnidaria, Hydrozoa) has emerged as a new experimental model animal in the last decade. Favorable characteristics include a fully transparent body suitable for microscopy, daily gamete production and a relatively short life cycle. Furthermore, whole genome sequence assembly and efficient gene editing techniques using CRISPR/Cas9 have opened new possibilities for genetic studies. The quasi-immortal vegetatively-growing polyp colony stage provides a practical means to maintain mutant strains. In the context of developing Clytia as a genetic model, we report here an improved whole life cycle culture method including an aquarium tank system designed for culture of the tiny jellyfish form. We have compared different feeding regimes using Artemia larvae as food and demonstrate that the stage-dependent feeding control is the key for rapid and reliable medusa and polyp rearing. Metamorphosis of the planula larvae into a polyp colony can be induced efficiently using a new synthetic peptide. The optimized procedures detailed here make it practical to generate genetically modified Clytia strains and to maintain their whole life cycle in the laboratory

Stress rotations and the long-term weakness of the Median Tectonic Line and the Rokko-Awaji Segment

International audienceWe used a field analysis of rock deformation microstructures and mesostructures to reconstructthe long-term orientation of stresses around two major active fault systems in Japan, the Median TectonicLine and the Rokko-Awaji Segment. Our study reveals that the dextral slip of the two fault systems, activesince the Plio-Quaternary, was preceded by fault normal extension in the Miocene and sinistral wrenching inthe Paleogene. The two fault systems deviated the regional stress field at the kilometer scale in their vicinityduring each of the three tectonic regimes. The largest deviation, found in the Plio-Quaternary, is a more faultnormal rotation of the maximum horizontal stress to an angle of 79° with the fault strands, suggesting anextremely low shear stress on the Median Tectonic Line and the Rokko-Awaji Segment. Possible causes of thislong-term stress perturbation include a nearly total release of shear stress during earthquakes, a low staticfriction coefficient, or lowelastic properties of the fault zones comparedwith the country rock. Independently ofthe preferred interpretation, the nearly fault normal orientation of the direction of maximum compressionsuggests that the mechanical properties of the fault zones are inadequate for the buildup of a pore fluidpressure sufficiently elevated to activate slip. The long-term weakness of the Median Tectonic Line and theRokko-Awaji Segment may reside in low-friction/low-elasticity materials or dynamic weakening rather than inpreearthquake fluid overpressures

Probabilistic Approach to One-Class Support Vector Machine

Classification is one of the main problem addressed by machine learning algorithms. Among them the Support Vector Machine (SVM) has attracted a lot of interest and shown success in the past decades. SVM are originally tailored for binary classification. If we have only a few example of negative dataset we can turn to one-class SVM. In this paper we propose a probabilistic interpretation of the one-class SVM approach and an extension especially adapted in the case of highly imbalanced dataset. Indeed, we consider a binary classification problem where we represent the negative dataset by its two first moments, while still modeling the positive class by individual examples. The optimization problem is shown to have an equivalent formulation to a one-class SVM applied to the positive dataset after some preprocess-ing. The usual one-class SVM corresponding to the case where the negative class has mean 0 and identity variance. We show empirically, on a protein classification task and a text classification task, that our approach achieves similar statistical performance than the two mainstream approaches to imbalanced classification problems , while being more computationally efficient

Smiles2Monomers: a link between chemical and biological structures for polymers

International audienceBackground: The monomeric composition of polymers is powerful for structure comparison and synthetic biology , among others. Many databases give access to the atomic structure of compounds but the monomeric structure of polymers is often lacking. We have designed a smart algorithm, implemented in the tool Smiles2Monomers (s2m), to infer efficiently and accurately the monomeric structure of a polymer from its chemical structure. Results: Our strategy is divided into two steps: first, monomers are mapped on the atomic structure by an efficient subgraph-isomorphism algorithm ; second, the best tiling is computed so that non-overlapping monomers cover all the structure of the target polymer. The mapping is based on a Markovian index built by a dynamic programming algorithm. The index enables s2m to search quickly all the given monomers on a target polymer. After, a greedy algorithm combines the mapped monomers into a consistent monomeric structure. Finally, a local branch and cut algorithm refines the structure. We tested this method on two manually annotated databases of polymers and reconstructed the structures de novo with a sensitivity over 90 %. The average computation time per polymer is 2 s. Conclusion: s2m automatically creates de novo monomeric annotations for polymers, efficiently in terms of time computation and sensitivity. s2m allowed us to detect annotation errors in the tested databases and to easily find the accurate structures. So, s2m could be integrated into the curation process of databases of small compounds to verify the current entries and accelerate the annotation of new polymers. The full method can be downloaded or accessed via a website for peptide-like polymers at http://bioinfo.lifl.fr/norine/smiles2monomers.jsp

Non Ribosomal Peptides: A monomeric puzzle

National audienceNonribosomal peptides (NRPs) are increasingly studied because they harbor activities which can be exploited in various domains. They are often denoted as graphs illustrating their chemical structure, where the atoms are represented by nodes and the chemical bonds by arcs. Another possible representation is the monomeric structure. This structure, inspired by the biosynthetic pathway of these peptides, is effectuated by large enzymatic complexes which assemble together smaller compounds called monomers. Consequently, the nonribosomal peptides are composed of a great variety of monomers (more than 500 are known) including amino acids, lipids and carbohydrates. Likewise, nonpetidic bonds are formed between multiple monomers, producing peptides with cycles and/or branches. Thus, the monomeric structure is a graph formed by the monomers present in the peptide and their interlinking chemical bonds. Until now, there did not exist a tool allowing for the conversion between the atomic and monomeric structures. This article presents a novel algorithm capable of localising the monomers from a reference list in the chemical structures of peptides extracted from the Norine database. The algorithm is based on a heuristic that utilizes chemical information of NRPs. The preliminary results are encouraging, and should lead to further studies.Les peptides non-ribosomiques (NRP) sont des molécules de plus en plus étudiées car elles présentent des activités ayant des applications principalement dans le domaine pharmaceutique. Elles sont souvent décrites par leur structure chimique, c'est-a-dire un graphe dont les noeuds sont des atomes et les arêtes les liaisons chimiques. Une autre représentation possible est la structure monomérique. Cette structure, inspirée de la voie de synthèse de ces peptides, est réalisé par de gros complexes enzymatiques qui assemblent les briques de base, appelées monomères. Ainsi, les peptides non-ribosomiques sont composés d'une grande variété de monomères (plus de 500 recensés jusqu'à présent) tels que des acides aminés, mais aussi des lipides ou des sucres. De plus, des liaisons non-peptidiques peuvent être formées entre certains monomères, ce qui produit des peptides contenant des cycles et/ou des branchements. La structure monomérique est donc le graphe formé par les monomères présents dans le peptide et les liaisons qui les relient. A l'heure actuelle, il n'existe pas d'outil permettant de convertir la structure chimique d'un peptide non-ribosomique en sa structure monomérique. Cet article présente un algorithme capable de localiser les monomères d'une liste de référence dans les structures chimiques des peptides de la base de données Norine. Il est basé sur une heuristique gloutonne qui utilise des connaissances sur la chimie des NRP. Les résultats préliminaires sont satisfaisants et devraient conduire à de nouvelles études

002 Évaluation de la toxicité des acides gras branchés sur des cellules conjonctivales en culture

Communication orale lors du 113e congrès de la Société Française d'Ophtalmologie.International audienc

Gelled Electrolyte Containing Phosphonium Ionic Liquids for Lithium-Ion Batteries

In this work, new gelled electrolytes were prepared based on a mixture containing phosphonium ionic liquid (IL) composed of trihexyl(tetradecyl)phosphonium cation combined with bis(trifluoromethane)sulfonimide [TFSI] counter anions and lithium salt, confined in a host network made from an epoxy prepolymer and amine hardener. We have demonstrated that the addition of electrolyte plays a key role on the kinetics of polymerization but also on the final properties of epoxy networks, especially thermal, thermo-mechanical, transport, and electrochemical properties. Thus, polymer electrolytes with excellent thermal stability (>300 °C) combined with good thermo-mechanical properties have been prepared. In addition, an ionic conductivity of 0.13 Ms·cm−1 at 100 °C was reached. Its electrochemical stability was 3.95 V vs. Li0/Li+ and the assembled cell consisting in Li|LiFePO4 exhibited stable cycle properties even after 30 cycles. These results highlight a promising gelled electrolyte for future lithium ion batteries