Long-term trends in trait structure of riverine communities facing predation risk increase and trophic resource decline.

Many large European rivers have undergone multiple pressures that have strongly impaired ecosystem functioning at different spatial and temporal scales. Global warming and other environmental changes have favored the success of invasive species, deeply modifying the structure of aquatic communities in large rivers. Some exogenous species could alter trophic interactions within assemblages by increasing the predation risk for potential prey species (top-down effect) and limiting the dynamics of others via resource availability limitation (bottom-up effect).

Meta-Analysis of Microarray Data of Rainbow Trout Fry Gonad Differentiation Modulated by Ethynylestradiol.

Sex differentiation in fish is a highly labile process easily reversed by the use of exogenous hormonal treatment and has led to environmental concerns since low doses of estrogenic molecules can adversely impact fish reproduction. The goal of this study was to identify pathways altered by treatment with ethynylestradiol (EE2) in developing fish and to find new target genes to be tested further for their possible role in male-to-female sex transdifferentiation. To this end, we have successfully adapted a previously developed bioinformatics workflow to a meta-analysis of two datasets studying sex reversal following exposure to EE2 in juvenile rainbow trout.

Adaptation of a Bioinformatics Microarray Analysis Workflow for a Toxicogenomic Study in Rainbow Trout.

Sex steroids play a key role in triggering sex differentiation in fish, the use of exogenous hormone treatment leading to partial or complete sex reversal. This phenomenon has attracted attention since the discovery that even low environmental doses of exogenous steroids can adversely affect gonad morphology (ovotestis development) and induce reproductive failure. Modern genomic-based technologies have enhanced opportunities to find out mechanisms of actions (MOA) and identify biomarkers related to the toxic action of a compound.

Intersex occurrence in rainbow trout (Oncorhynchus mykiss) male fry chronically exposed to ethynylestradiol.

This study aimed to investigate the male-to-female morphological and physiological transdifferentiation process in rainbow trout (Oncorhynchus mykiss) exposed to exogenous estrogens. The first objective was to elucidate whether trout develop intersex gonads under exposure to low levels of estrogen. To this end, the gonads of an all-male population of fry exposed chronically (from 60 to 136 days post fertilization--dpf) to several doses (from environmentally relevant 0.

Meta-analysis and gene set analysis of archived microarrays suggest implication of the spliceosome in metastatic and hypoxic phenotypes.

We propose to make use of the wealth of underused DNA chip data available in public repositories to study the molecular mechanisms behind the adaptation of cancer cells to hypoxic conditions leading to the metastatic phenotype. We have developed new bioinformatics tools and adapted others to identify with maximum sensitivity those genes which are expressed differentially across several experiments. The comparison of two analytical approaches, based on either Over Representation Analysis or Functional Class Scoring, by a meta-analysis-based approach, led to the retrieval of known information about the biological situation - thus validating the model - but also more importantly to the discovery of the previously unknown implication of the spliceosome, the cellular machinery responsible for mRNA splicing, in the development of metastasis.

A study of the anatomy and injection techniques of the ovine stifle by positive contrast arthrography, computed tomography arthrography and gross anatomical dissection.

Although ovine stifle models are commonly used to study osteoarthritis, meniscal pathology and cruciate ligament injuries and repair, there is little information about the anatomy of the joint or techniques for synovial injections. The objectives of this study were to improve anatomical knowledge of the synovial cavities of the ovine knee and to compare intra-articular injection techniques. Synovial cavities of 24 cadaver hind limbs from 12 adult sheep were investigated by intra-articular resin, positive-contrast arthrography, computed tomography (CT) arthrography and gross anatomical dissection.

gViz, a novel tool for the visualization of co-expression networks.

Background: The quantity of microarray data available on the Internet has grown dramatically over the past years and now represents millions of Euros worth of underused information. One way to use this data is through co-expression analysis. To avoid a certain amount of bias, such data must often be analyzed at the genome scale, for example by network representation.

PathEx: a novel multi factors based datasets selector web tool.

Background: Microarray experiments have become very popular in life science research. However, if such experiments are only considered independently, the possibilities for analysis and interpretation of many life science phenomena are reduced. The accumulation of publicly available data provides biomedical researchers with a valuable opportunity to either discover new phenomena or improve the interpretation and validation of other phenomena that partially understood or well known.

Functional analysis: evaluation of response intensities--tailoring ANOVA for lists of expression subsets.

Background: Microarray data is frequently used to characterize the expression profile of a whole genome and to compare the characteristics of that genome under several conditions. Geneset analysis methods have been described previously to analyze the expression values of several genes related by known biological criteria (metabolic pathway, pathology signature, co-regulation by a common factor, etc.) at the same time and the cost of these methods allows for the use of more values to help discover the underlying biological mechanisms.

Transcriptional profiling after lipid raft disruption in keratinocytes identifies critical mediators of atopic dermatitis pathways.

Lipid rafts are cholesterol-rich cell signaling platforms, and their physiological role can be explored by cholesterol depletion. To characterize transcriptional changes ongoing after lipid raft disruption in epidermal keratinocytes, a cell type that synthesizes its cholesterol in situ, we performed whole-genome expression profiling. Microarray results show that over 3,000 genes are differentially regulated.

Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells.

Background: Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear.

2x genomes--depth does matter.

Background: Given the availability of full genome sequences, mapping gene gains, duplications, and losses during evolution should theoretically be straightforward. However, this endeavor suffers from overemphasis on detecting conserved genome features, which in turn has led to sequencing multiple eutherian genomes with low coverage rather than fewer genomes with high-coverage and more even distribution in the phylogeny. Although limitations associated with analysis of low coverage genomes are recognized, they have not been quantified.

A benchmark for statistical microarray data analysis that preserves actual biological and technical variance.

Background: Recent reanalysis of spike-in datasets underscored the need for new and more accurate benchmark datasets for statistical microarray analysis. We present here a fresh method using biologically-relevant data to evaluate the performance of statistical methods.

Results: Our novel method ranks the probesets from a dataset composed of publicly-available biological microarray data and extracts subset matrices with precise information/noise ratios.

Design and implementation of a database for Brucella melitensis genome annotation.

The genome sequences of three Brucella biovars and of some species close to Brucella sp. have become available, leading to new relationship analysis. Moreover, the automatic genome annotation of the pathogenic bacteria Brucella melitensis has been manually corrected by a consortium of experts, leading to 899 modifications of start sites predictions among the 3198 open reading frames (ORFs) examined.

Cortisol and behavioral responses of working dogs to environmental challenges.

This paper's primary objective is to analyse the physiological (cortisol) and behavioral responses of military working dogs (MWD). Dogs (N=27) were submitted twice to environmental challenges (challenge 1 and 2, 20 days in-between) composed of social (training), visual (mobile toy car) and auditory (air blast) stimuli. Cortisol levels decreased back to the baseline after the second challenge.

Identification, cloning, and expression of the Scytalidium acidophilum XYL1 gene encoding for an acidophilic xylanase.

We cloned XYL1, a Scytalidium acidophilum gene encoding for an acidophilic family 11 xylanase. The XYL1p protein was expressed in Pichia pastoris using the pPICZalphaA expression plasmid. The secreted protein was purified by TAXI affinity column chromatography.

Adenylation-dependent conformation and unfolding pathways of the NAD+-dependent DNA ligase from the thermophile Thermus scotoductus.

In the last few years, an increased attention has been focused on NAD(+)-dependent DNA ligases. This is mostly due to their potential use as antibiotic targets, because effective inhibition of these essential enzymes would result in the death of the bacterium. However, development of an efficient drug requires that the conformational modifications involved in the catalysis of NAD(+)-dependent DNA ligases are understood.

Modeling of human monoamine oxidase A: from low resolution threading models to accurate comparative models based on crystal structures.

The recently published crystal structure of monoamine oxidase (MAO) B was a major breakthrough for structural and functional understanding of flavin containing amine oxidases: it opens a new era of research and provides new opportunities to those interested in the biochemistry and pharmacology of those important drug targets. In particular, it allowed accurate modeling of human MAO A, both proteins sharing over 70% sequence identity. In the present contribution, we summarize the efforts made in order to obtain structural information on the human MAO A, including sequence analysis, secondary structure predictions, and preliminary models obtained by fold recognition and comparative modeling based on proteins sharing low sequence identity.

Cofactor binding modulates the conformational stabilities and unfolding patterns of NAD(+)-dependent DNA ligases from Escherichia coli and Thermus scotoductus.

DNA ligases are important enzymes required for cellular processes such as DNA replication, recombination, and repair. NAD(+)-dependent DNA ligases are essentially restricted to eubacteria, thus constituting an attractive target in the development of novel antibiotics. Although such a project might involve the systematic testing of a vast number of chemical compounds, it can essentially gain from the preliminary deciphering of the conformational stability and structural perturbations associated with the formation of the catalytically active adenylated enzyme.

Structural and functional adaptations to extreme temperatures in psychrophilic, mesophilic, and thermophilic DNA ligases.

Psychrophiles, host of permanently cold habitats, display metabolic fluxes comparable to those exhibited by mesophilic organisms at moderate temperatures. These organisms have evolved by producing, among other peculiarities, cold-active enzymes that have the properties to cope with the reduction of chemical reaction rates induced by low temperatures. The emerging picture suggests that these enzymes display a high catalytic efficiency at low temperatures through an improved flexibility of the structural components involved in the catalytic cycle, whereas other protein regions, if not implicated in catalysis, may be even more rigid than their mesophilic counterparts.

ESyPred3D: Prediction of proteins 3D structures.

Motivation: Homology or comparative modeling is currently the most accurate method to predict the three-dimensional structure of proteins. It generally consists in four steps: (1) databanks searching to identify the structural homolog, (2) target-template alignment, (3) model building and optimization, and (4) model evaluation. The target-template alignment step is generally accepted as the most critical step in homology modeling.

The endoxylanases from family 11: computer analysis of protein sequences reveals important structural and phylogenetic relationships.

Eighty-two amino acid sequences of the catalytic domains of mature endoxylanases belonging to family 11 have been aligned using the programs MATCHBOX and CLUSTAL. The sequences range in length from 175 to 233 residues. The two glutamates acting as catalytic residues are conserved in all sequences.

Crystallographic analysis of family 11 endo-beta-1,4-xylanase Xyl1 from Streptomyces sp. S38.

Family 11 endo-beta-1,4-xylanases degrade xylan, the main constituent of plant hemicelluloses, and have many potential uses in biotechnology. The structure of Xyl1, a family 11 endo-xylanase from Streptomyces sp. S38, has been solved.

Structural approach of human MAO-A using fold recognition (threading) techniques.

The major goal of the present work is to further approach the structure of human monoamine oxidase A (MAO-A). A first partial three-dimensional model of human MAO-A has already been established using secondary structure predictions and fold recognition methods [Wouters and Baudoux, 1998]. In this modeled structure, a segment of the sequence (residues 369-393) located near the covalent linkage to the essential flavin cofactor, and potentially involved in the structure of the active site of the protein, could not be modeled.

Topology prediction of Brucella abortus Omp2b and Omp2a porins after critical assessment of transmembrane beta strands prediction by several secondary structure prediction methods.

In order to propose a reliable model for Brucella porin topology, several structure prediction methods were evaluated in their ability to predict porin topology. Four porins of known structure were selected as test-cases and their secondary structure delineated. The specificity and sensitivity of 11 methods were separately evaluated.