Structures tertiaires protéomimétiques issues d'oligoamides aromatiques

Des oligoamides constitués d’unités dérivées de la quinoline ont été conçus pour adopter des conformations hélicoïdales bien définies et très stables. Dans une première partie, la stabilité de ces structures a été modulée par l’incorporation d’unités pyridines présentant une fonction aminométhyle. La structure cristalline d’un hybride aromatique-aliphatique synthétique a révélé un repliement original en hélice non canonique. Des études par RMN approfondies ont confirmé l’existence de cette conformation en solution, mais celle-ci n’est vraisemblablement pas l’unique conformation présente. Dans une seconde partie, des structures tertiaires protéomimétiques en faisceaux d’hélices ont été conçues et synthétisées à partir de foldamères d’oligoamides aromatiques. Dans ces structures, les hélices sont connectées par différents liens qui imposent des géométries et des symétries diverses. Des interactions tertiaires entre les chaînes latérales de certains résidus ont pu être caractérisées dans le solide et en solution. Les composés obtenus ressemblent tant par leur taille (4-8 kDa) que par leur complexité structurale à de petites protéines. D’autres structures tertiaires ont été obtenues dynamiquement en utilisant la chimie de coordination. Pour ce faire, des foldamères ont été fonctionnalisés à leur extrémité C ou N terminale par une fonction amine. Au cours d’une seule étape de synthèse, des ligands imines, issus de la condensation de ces amines sur différents aldéhydes ont été formés autour de cuivre I. Une forme de communication entre les hélices et le métal central a alors pu être mise en évidence par RMN et dans un cas par diffraction des rayons X.Quinoline-derived oligoamide foldamers have been designed to adopt well-defined helical conformations. This peptidomimetic secondary structure is extremely stable. In a first part, some flexibility has been introduced to these oligomers by incorporating pyridine-derived monomers bearing an aliphatic amine. The resultant aromatic-aliphatic hybrid adopts an original herringbone helical conformation in the solid state. NMR experiments similar to those developed for solving the structures of peptides have confirmed the presence of this conformation in solution as well. In a second part, proteomimetic tertiary structures (bundles) have been designed and synthesized using aromatic oligoamide foldamers. The helices are connected by different linkers that impose different geometries and symetries. Tertiary interactions between peripheral residues have been characterized both in liquid and solid states. The folded synthetic molecules ressemble to small proteins in terms of size (4-8 kDa) and structural complexity. Other tertiary structures have been generated dynamically by using metal coordination. For that purpose, quinoline-derived foldamers have been functionalized at their C or Nterminus by an amine residue. In a one-pot reaction imine ligands made from the foldamers with different aldehydes have been formed around copper I. The communication between the helices and the metal was then characterized by NMR and in one case by X-ray diffraction

Heterotachy and long-branch attraction in phylogenetics

BACKGROUND: Probabilistic methods have progressively supplanted the Maximum Parsimony (MP) method for inferring phylogenetic trees. One of the major reasons for this shift was that MP is much more sensitive to the Long Branch Attraction (LBA) artefact than is Maximum Likelihood (ML). However, recent work by Kolaczkowski and Thornton suggested, on the basis of simulations, that MP is less sensitive than ML to tree reconstruction artefacts generated by heterotachy, a phenomenon that corresponds to shifts in site-specific evolutionary rates over time. These results led these authors to recommend that the results of ML and MP analyses should be both reported and interpreted with the same caution. This specific conclusion revived the debate on the choice of the most accurate phylogenetic method for analysing real data in which various types of heterogeneities occur. However, variation of evolutionary rates across species was not explicitly incorporated in the original study of Kolaczkowski and Thornton, and in most of the subsequent heterotachous simulations published to date, where all terminal branch lengths were kept equal, an assumption that is biologically unrealistic. RESULTS: In this report, we performed more realistic simulations to evaluate the relative performance of MP and ML methods when two kinds of heterogeneities are considered: (i) within-site rate variation (heterotachy), and (ii) rate variation across lineages. Using a similar protocol as Kolaczkowski and Thornton to generate heterotachous datasets, we found that heterotachy, which constitutes a serious violation of existing models, decreases the accuracy of ML whatever the level of rate variation across lineages. In contrast, the accuracy of MP can either increase or decrease when the level of heterotachy increases, depending on the relative branch lengths. This result demonstrates that MP is not insensitive to heterotachy, contrary to the report of Kolaczkowski and Thornton. Finally, in the case of LBA (i.e. when two non-sister lineages evolved faster than the others), ML outperforms MP over a wide range of conditions, except for unrealistic levels of heterotachy. CONCLUSION: For realistic combinations of both heterotachy and variation of evolutionary rates across lineages, ML is always more accurate than MP. Therefore, ML should be preferred over MP for analysing real data, all the more so since parametric methods also allow one to handle other types of biological heterogeneities much better, such as among sites rate variation. The confounding effects of heterotachy on tree reconstruction methods do exist, but can be eschewed by the development of mixture models in a probabilistic framework, as proposed by Kolaczkowski and Thornton themselves

PhyloExplorer: a web server to validate, explore and query phylogenetic trees

<p>Abstract</p> <p>Background</p> <p>Many important problems in evolutionary biology require molecular phylogenies to be reconstructed. Phylogenetic trees must then be manipulated for subsequent inclusion in publications or analyses such as supertree inference and tree comparisons. However, no tool is currently available to facilitate the management of tree collections providing, for instance: standardisation of taxon names among trees with respect to a reference taxonomy; selection of relevant subsets of trees or sub-trees according to a taxonomic query; or simply computation of descriptive statistics on the collection. Moreover, although several databases of phylogenetic trees exist, there is currently no easy way to find trees that are both relevant and complementary to a given collection of trees.</p> <p>Results</p> <p>We propose a tool to facilitate assessment and management of phylogenetic tree collections. Given an input collection of rooted trees, PhyloExplorer provides facilities for obtaining statistics describing the collection, correcting invalid taxon names, extracting taxonomically relevant parts of the collection using a dedicated query language, and identifying related trees in the TreeBASE database.</p> <p>Conclusion</p> <p>PhyloExplorer is a simple and interactive website implemented through underlying Python libraries and MySQL databases. It is available at: <url>http://www.ncbi.orthomam.univ-montp2.fr/phyloexplorer/</url> and the source code can be downloaded from: <url>http://code.google.com/p/taxomanie/</url>.</p

Instantaneous frequency and amplitude of complex signals based on quaternion Fourier transform

The ideas of instantaneous amplitude and phase are well understood for signals with real-valued samples, based on the analytic signal which is a complex signal with one-sided Fourier transform. We extend these ideas to signals with complex-valued samples, using a quaternion-valued equivalent of the analytic signal obtained from a one-sided quaternion Fourier transform which we refer to as the hypercomplex representation of the complex signal. We present the necessary properties of the quaternion Fourier transform, particularly its symmetries in the frequency domain and formulae for convolution and the quaternion Fourier transform of the Hilbert transform. The hypercomplex representation may be interpreted as an ordered pair of complex signals or as a quaternion signal. We discuss its derivation and properties and show that its quaternion Fourier transform is one-sided. It is shown how to derive from the hypercomplex representation a complex envelope and a phase. A classical result in the case of real signals is that an amplitude modulated signal may be analysed into its envelope and carrier using the analytic signal provided that the modulating signal has frequency content not overlapping with that of the carrier. We show that this idea extends to the complex case, provided that the complex signal modulates an orthonormal complex exponential. Orthonormal complex modulation can be represented mathematically by a polar representation of quaternions previously derived by the authors. As in the classical case, there is a restriction of non-overlapping frequency content between the modulating complex signal and the orthonormal complex exponential. We show that, under these conditions, modulation in the time domain is equivalent to a frequency shift in the quaternion Fourier domain. Examples are presented to demonstrate these concepts

New insight into the structural, electrochemical and biological aspects of macrocylic Cu(II) complexes derived from S-substituted dithiocarbazate Schiff bases

Copper (II) complexes synthesized from the products of condensation of S-methyl- and S-benzyldithiocarbazate with 2,5-hexanedione (SMHDH2 and SBHDH2 respectively) have been characterized using various physicochemical (elemental analysis, molar conductivity, magnetic susceptibility) and spectroscopic (infrared, electronic) methods. The structures of SMHDH2, its copper (II) complex, CuSMHD, and the related CuSBHD complex as well as a pyrrole byproduct, SBPY, have been determined by single crystal X-ray diffraction. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. Antibacterial activity and cytotoxicity were evaluated. The compounds, dissolved in 0.5% and 5% DMSO, showed a wide range of antibacterial activity against 10 strains of Gram-positive and Gram-negative bacteria. Investigations of the effects of efflux pumps and membrane penetration on antibacterial activity are reported herein. Antiproliferation activity was observed to be enhanced by complexation with copper. Preliminary screening showed Cu complexes are strongly active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7

Acoel Flatworms Are Not Platyhelminthes: Evidence from Phylogenomics

Acoel flatworms are small marine worms traditionally considered to belong to the phylum Platyhelminthes. However, molecular phylogenetic analyses suggest that acoels are not members of Platyhelminthes, but are rather extant members of the earliest diverging Bilateria. This result has been called into question, under suspicions of a long branch attraction (LBA) artefact. Here we re-examine this problem through a phylogenomic approach using 68 different protein-coding genes from the acoel Convoluta pulchra and 51 metazoan species belonging to 15 different phyla. We employ a mixture model, named CAT, previously found to overcome LBA artefacts where classical models fail. Our results unequivocally show that acoels are not part of the classically defined Platyhelminthes, making the latter polyphyletic. Moreover, they indicate a deuterostome affinity for acoels, potentially as a sister group to all deuterostomes, to Xenoturbellida, to Ambulacraria, or even to chordates. However, the weak support found for most deuterostome nodes, together with the very fast evolutionary rate of the acoel Convoluta pulchra, call for more data from slowly evolving acoels (or from its sister-group, the Nemertodermatida) to solve this challenging phylogenetic problem

Sustainable computational science: the ReScience initiative

Computer science o ers a large set of tools for prototyping, writing, running, testing, validating, sharing and reproducing results, however computational science lags behind. In the best case, authors may provide their source code as a compressed archive and they may feel con dent their research is reproducible. But this is not exactly true. Jonathan Buckheit and David Donoho proposed more than two decades ago that an article about computational results is advertising, not scholarship. e actual scholarship is the full so ware environment, code, and data that produced the result. is implies new work ows, in particular in peer-reviews. Existing journals have been slow to adapt: source codes are rarely requested, hardly ever actually executed to check that they produce the results advertised in the article. ReScience is a peer-reviewed journal that targets computational research and encourages the explicit replication of already published research, promoting new and open-source implementations in order to ensure that the original research can be replicated from its description. To achieve this goal, the whole publishing chain is radically di erent from other traditional scienti c journals. ReScience resides on GitHub where each new implementation of a computational study is made available together with comments, explanations, and so ware tests

A Multicassette Gateway Vector Set for High Throughput and Comparative Analyses in Ciona and Vertebrate Embryos

BACKGROUND: The past few years have seen a vast increase in the amount of genomic data available for a growing number of taxa, including sets of full length cDNA clones and cis-regulatory sequences. Large scale cross-species comparisons of protein function and cis-regulatory sequences may help to understand the emergence of specific traits during evolution. PRINCIPAL FINDINGS: To facilitate such comparisons, we developed a Gateway compatible vector set, which can be used to systematically dissect cis-regulatory sequences, and overexpress wild type or tagged proteins in a variety of chordate systems. It was developed and first characterised in the embryos of the ascidian Ciona intestinalis, in which large scale analyses are easier to perform than in vertebrates, owing to the very efficient embryo electroporation protocol available in this organism. Its use was then extended to fish embryos and cultured mammalian cells. CONCLUSION: This versatile vector set opens the way to the mid- to large-scale comparative analyses of protein function and cis-regulatory sequences across chordate evolution. A complete user manual is provided as supplemental material

A Phylogenetic Perspective on the Evolution of Mediterranean Teleost Fishes

The Mediterranean Sea is a highly diverse, highly studied, and highly impacted biogeographic region, yet no phylogenetic reconstruction of fish diversity in this area has been published to date. Here, we infer the timing and geographic origins of Mediterranean teleost species diversity using nucleotide sequences collected from GenBank. We assembled a DNA supermatrix composed of four mitochondrial genes (12S ribosomal DNA, 16S ribosomal DNA, cytochrome c oxidase subunit I and cytochrome b) and two nuclear genes (rhodopsin and recombination activating gene I), including 62% of Mediterranean teleost species plus 9 outgroups. Maximum likelihood and Bayesian phylogenetic and dating analyses were calibrated using 20 fossil constraints. An additional 124 species were grafted onto the chronogram according to their taxonomic affinity, checking for the effects of taxonomic coverage in subsequent diversification analyses. We then interpreted the time-line of teleost diversification in light of Mediterranean historical biogeography, distinguishing non-endemic natives, endemics and exotic species. Results show that the major Mediterranean orders are of Cretaceous origin, specifically ∼100–80 Mya, and most Perciformes families originated 80–50 Mya. Two important clade origin events were detected. The first at 100–80 Mya, affected native and exotic species, and reflects a global diversification period at a time when the Mediterranean Sea did not yet exist. The second occurred during the last 50 Mya, and is noticeable among endemic and native species, but not among exotic species. This period corresponds to isolation of the Mediterranean from Indo-Pacific waters before the Messinian salinity crisis. The Mediterranean fish fauna illustrates well the assembly of regional faunas through origination and immigration, where dispersal and isolation have shaped the emergence of a biodiversity hotspot