4D experiments measured with APSY for automated backbone resonance assignments of large proteins

Detailed structural and functional characterization of proteins by solution NMR requires sequence-specific resonance assignment. We present a set of transverse relaxation optimization (TROSY) based four-dimensional automated projection spectroscopy (APSY) experiments which are designed for resonance assignments of proteins with a size up to 40kDa, namely HNCACO, HNCOCA, HNCACB and HN(CO)CACB. These higher-dimensional experiments include several sensitivity-optimizing features such as multiple quantum parallel evolution in a ‘just-in-time' manner, aliased off-resonance evolution, evolution-time optimized APSY acquisition, selective water-handling and TROSY. The experiments were acquired within the concept of APSY, but they can also be used within the framework of sparsely sampled experiments. The multidimensional peak lists derived with APSY provided chemical shifts with an approximately 20 times higher precision than conventional methods usually do, and allowed the assignment of 90% of the backbone resonances of the perdeuterated primase-polymerase ORF904, which contains 331 amino acid residues and has a molecular weight of 38.4kD

Construction d'une plate-forme intégrée pour la cartographie de l'exposition des populations aux substances chimiques de l'environnement

National audienceAnalysis of the association between the environment and health has become a major public health concern, as shown by the development of two national environmental health plans. For such an analysis, policy-makers need tools to identify the geographic areas where overexposure to toxic agents may be observed. The objective of the SIGFRIED 1 project is to build a work station for spatial modeling of the exposure of the French population to chemical substances and for identifying the determinants of this exposure. Probabilistic multimedia modeling is used to assess exposure. The epistemological problems associated with the absence of data are overcome by the implementation of tools that apply spatial analysis techniques. An example is furnished for the region of Nord-Pas-de-Calais and Picardie, for cadmium, nickel and lead exposure. The calculation of exposure is performed for duration of 70 years on the basis of data collected around 2004 fora grid of squares 1 km in length. For example, for Nord-Pas-de-Calais, the indicators allow us to define two areas for cadmium and three for lead. They are linked to the region's industrial history: mining basin, metallurgy activities, and the Lille metropolitan area. The contribution of various exposure pathways varied substantially from one pollutant to another. The exposure maps thus obtained allow us to identify the geographic area where environmental studies must be conducted in priority. The GIS thus constructed is the foundation of a workstation where source emission data, environmental exposure measurements, and finally health and socioeconomic measurements can be combined.L'analyse du lien entre l'environnement et la santé est devenue une préoccupation majeure de santé publique comme en témoigne l'émergence des deux Plans nationaux santé environnement. Pour ce faire, les décideurs sont confrontés au besoin de développement d'outils nécessaires à l'identification des zones géographiques dans lesquelles une surexposition potentielle à des substances toxiques est observée. L'objectif du projet Système d'information géographique (SIG), facteurs de risques environnementaux et décès par cancer (SIGFRIED 1) est de construire une plate-forme de modélisation permettant d'évaluer, par une approche spatiale, l'exposition de la population française aux substances chimiques et d'en identifier ses déterminants. L'évaluation des expositions est réalisée par le biais d'une modélisation multimédia probabiliste. Les problèmes épistémologiques liés à l'absence de données sont palliés par la mise en œuvre d'outils utilisant les techniques d'analyse spatiale. Un exemple est fourni sur la région Nord-Pas-de-Calais et Picardie, pour le cadmium, le nickel et le plomb. Le calcul de l'exposition est réalisé sur une durée de 70 ans sur la base des données disponibles autour de l'année 2004 sur une maille de 1 km de côté. Par exemple pour le Nord-Pas-de-Calais, les indicateurs permettent de définir deux zones pour le cadmium et trois zones pour le plomb. Celles-ci sont liées à l'historique industriel de la région : le bassin minier, les activités métallurgiques et l'agglomération lilloise. La contribution des différentes voies d'exposition varie sensiblement d'un polluant à l'autre. Les cartes d'exposition ainsi obtenues permettent d'identifier les zones géographiques dans lesquelles conduire en priorité des études environnementales de terrains. Le SIG construit constitue la base d'une plate-forme où les données d'émission à la source, de mesures environnementales, d'exposition, puis sanitaires et socio-économiques pourront être associées

Computer vision-based automated peak picking applied to protein NMR spectra

Motivation: A detailed analysis of multidimensional NMR spectra of macromolecules requires the identification of individual resonances (peaks). This task can be tedious and time-consuming and often requires support by experienced users. Automated peak picking algorithms were introduced more than 25 years ago, but there are still major deficiencies/flaws that often prevent complete and error free peak picking of biological macromolecule spectra. The major challenges of automated peak picking algorithms is both the distinction of artifacts from real peaks particularly from those with irregular shapes and also picking peaks in spectral regions with overlapping resonances which are very hard to resolve by existing computer algorithms. In both of these cases a visual inspection approach could be more effective than a ‘blind' algorithm. Results: We present a novel approach using computer vision (CV) methodology which could be better adapted to the problem of peak recognition. After suitable ‘training' we successfully applied the CV algorithm to spectra of medium-sized soluble proteins up to molecular weights of 26 kDa and to a 130 kDa complex of a tetrameric membrane protein in detergent micelles. Our CV approach outperforms commonly used programs. With suitable training datasets the application of the presented method can be extended to automated peak picking in multidimensional spectra of nucleic acids or carbohydrates and adapted to solid-state NMR spectra. Availability and implementation: CV-Peak Picker is available upon request from the authors. Contact: [email protected]; [email protected]; [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

A multi-modal perception based assistive robotic system for the elderly

Edited by Giovanni Maria Farinella, Takeo Kanade, Marco Leo, Gerard G. Medioni, Mohan TrivediInternational audienceIn this paper, we present a multi-modal perception based framework to realize a non-intrusive domestic assistive robotic system. It is non-intrusive in that it only starts interaction with a user when it detects the user's intention to do so. All the robot's actions are based on multi-modal perceptions which include user detection based on RGB-D data, user's intention-for-interaction detection with RGB-D and audio data, and communication via user distance mediated speech recognition. The utilization of multi-modal cues in different parts of the robotic activity paves the way to successful robotic runs (94% success rate). Each presented perceptual component is systematically evaluated using appropriate dataset and evaluation metrics. Finally the complete system is fully integrated on the PR2 robotic platform and validated through system sanity check runs and user studies with the help of 17 volunteer elderly participants

Conformational and thermodynamic changes of the repressor/DNA operator complex upon monomerization shed new light on regulation mechanisms of bacterial resistance against β-lactam antibiotics

In absence of β-lactam antibiotics, BlaI and MecI homodimeric repressors negatively control the expression of genes involved in β-lactam resistance in Bacillus licheniformis and in Staphylococcus aureus. Subsequently to β-lactam presence, BlaI/MecI is inactivated by a single-point proteolysis that separates its N-terminal DNA-binding domain to its C-terminal domain responsible for its dimerization. Concomitantly to this proteolysis, the truncated repressor acquires a low affinity for its DNA target that explains the expression of the structural gene for resistance. To understand the loss of the high DNA affinity of the truncated repressor, we have determined the different dissociation constants of the system and solved the solution structure of the B. licheniformis monomeric repressor complexed to the semi-operating sequence OP1 of blaP (1/2OP1blaP) by using a de novo docking approach based on inter-molecular nuclear Overhauser effects and chemical-shift differences measured on each macromolecular partner. Although the N-terminal domain of the repressor is not subject to internal structural rearrangements upon DNA binding, the molecules adopt a tertiary conformation different from the crystallographic operator–repressor dimer complex, leading to a 30° rotation of the monomer with respect to a central axis extended across the DNA

How to measure sedentary behavior at work?

Background: Prolonged sedentary behavior (SB) is associated with increased risk for chronic conditions. A growing number of the workforce is employed in office setting with high occupational exposure to SB. There is a new focus in assessing, understanding and reducing SB in the workplace. There are many subjective (questionnaires) and objective methods (monitoring with wearable devices) available to determine SB. Therefore, we aimed to provide a global understanding on methods currently used for SB assessment at work.Methods: We carried out a systematic review on methods to measure SB at work. Pubmed, Cochrane, Embase, and Web of Science were searched for peer-reviewed English-language articles published between 1st January 2000 and 17th March 2019.Results: We included 154 articles: 89 were cross-sectional and 65 were longitudinal studies, for a total of 474,091 participants. SB was assessed by self-reported questionnaires in 91 studies, by wearables devices in also 91 studies, and simultaneously by a questionnaire and wearables devices in 30 studies. Among the 91 studies using wearable devices, 73 studies used only one device, 15 studies used several devices, and three studies used complex physiological systems. Studies exploring SB on a large sample used significantly more only questionnaires and/or one wearable device.Conclusions: Available questionnaires are the most accessible method for studies on large population with a limited budget. For smaller groups, SB at work can be objectively measured with wearable devices (accelerometers, heart-rate monitors, pressure meters, goniometers, electromyography meters, gas-meters) and the results can be associated and compared with a subjective measure (questionnaire). The number of devices worn can increase the accuracy but make the analysis more complex and time consuming

A Peptidoglycan Fragment Triggers β-lactam Resistance in Bacillus licheniformis

To resist to β-lactam antibiotics Eubacteria either constitutively synthesize a β-lactamase or a low affinity penicillin-binding protein target, or induce its synthesis in response to the presence of antibiotic outside the cell. In Bacillus licheniformis and Staphylococcus aureus, a membrane-bound penicillin receptor (BlaR/MecR) detects the presence of β-lactam and launches a cytoplasmic signal leading to the inactivation of BlaI/MecI repressor, and the synthesis of a β-lactamase or a low affinity target. We identified a dipeptide, resulting from the peptidoglycan turnover and present in bacterial cytoplasm, which is able to directly bind to the BlaI/MecI repressor and to destabilize the BlaI/MecI-DNA complex. We propose a general model, in which the acylation of BlaR/MecR receptor and the cellular stress induced by the antibiotic, are both necessary to generate a cell wall-derived coactivator responsible for the expression of an inducible β-lactam-resistance factor. The new model proposed confirms and emphasizes the role of peptidoglycan degradation fragments in bacterial cell regulation

Present eternity : quests of temporality in the literary production of the "extrême contemporain" in France (The Writings of Dominique Fourcade and Emmanuel Hocquard)

The term \uab extr\ueame contemporain \ubb is an expression currently used by scholars to indicate the French literary production of the last 20 years. This term was used in a work of literature for the first time by the French poet Dominique Fourcade in 1986 (\uc9l\ue9gie L apostrophe E.C.) in reference to an epoch, but also to a new sense of experiencing time and space in the so-called \uab age of digital reproducibility \ubb. The aim of this paper is to consider how the change in temporal protocols due to the triumph of Big Optics (Paul Virilio) affects the sense of teleology (destiny) and the quest for experience in French contemporary poetry (in particular, in the genre of the elegy). Including both memory and anticipation, the \uab extr\ueame contemporain \ubb production seems to prefer the \u201ctime of now\u201d, Jetz-zeit in Benjamin\u2019s words, to past or testimony, and speaks to the present, whose responsibility is to give voice to a space where everything is simply allowed to happen

ADNL: Accurate Distributed Node Localization Algorithm in Wireless Sensor Networks

International audienceThis paper deals with the multi-hop localization problem in static Wireless Sensor Networks. The knowledge of geographical positions of nodes is useful in such networks, as it can be used in communication protocols or to provide geographical information of detected events. We present in this paper a new and original method to locate sensor nodes, named ADNL. In our method, each sensor knows anchor nodes positions in its k-hop neighborhood and also distance between neighbor nodes thanks to a technology like TDoA. Nodes with enough anchors in their neighborhood locally run a force-based algorithm so as to deduce their position, and then forward it so as to enable other nodes to locate themselves. We provide extensive simulations under various network topologies, densities, number of anchor nodes and distance estimation errors, so as to present results showing the accuracy of our localization algorithm. ADNL algorithm is shown to be particularly accurate and robust to both distance estimation errors and irregular topologies