Structure and Function of the First Full-Length Murein Peptide Ligase (Mpl) Cell Wall Recycling Protein

Bacterial cell walls contain peptidoglycan, an essential polymer made by enzymes in the Mur pathway. These proteins are specific to bacteria, which make them targets for drug discovery. MurC, MurD, MurE and MurF catalyze the synthesis of the peptidoglycan precursor UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-diaminopimelyl-D-alanyl-D-alanine by the sequential addition of amino acids onto UDP-N-acetylmuramic acid (UDP-MurNAc). MurC-F enzymes have been extensively studied by biochemistry and X-ray crystallography. In Gram-negative bacteria, ∼30–60% of the bacterial cell wall is recycled during each generation. Part of this recycling process involves the murein peptide ligase (Mpl), which attaches the breakdown product, the tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, to UDP-MurNAc. We present the crystal structure at 1.65 Å resolution of a full-length Mpl from the permafrost bacterium Psychrobacter arcticus 273-4 (PaMpl). Although the Mpl structure has similarities to Mur enzymes, it has unique sequence and structure features that are likely related to its role in cell wall recycling, a function that differentiates it from the MurC-F enzymes. We have analyzed the sequence-structure relationships that are unique to Mpl proteins and compared them to MurC-F ligases. We have also characterized the biochemical properties of this enzyme (optimal temperature, pH and magnesium binding profiles and kinetic parameters). Although the structure does not contain any bound substrates, we have identified ∼30 residues that are likely to be important for recognition of the tripeptide and UDP-MurNAc substrates, as well as features that are unique to Psychrobacter Mpl proteins. These results provide the basis for future mutational studies for more extensive function characterization of the Mpl sequence-structure relationships

Gestion des déchets ménagers : comment les collectivités françaises mobilisent-elles leurs usagers ?

L’objectif de cette recherche est d’étudier les mesures développées par les collectivités territoriales pour encourager les ménages à adopter des comportements pro-environnementaux. Notre approche articule deux démarches complémentaires.D’une part, à partir d’une approche économique, nous analysons les choix des collectivités territoriales pour inciter les usagers du service d’élimination des déchets ménagers à jeter moins de déchets. Dans ce cadre, nous avons élaboré une typologie des leviers d’action développés par les collectivités territoriales. Quatre types de stratégies d’implication différentes des usagers ont été identifiés auprès de collectivités territoriales françaises, décrivant des combinaisons de mesures particulières pour atteindre les objectifs environnementaux fixés par la politique nationale des déchets. Puis, à partir d’une étude économétrique, nous avons mis en évidence l’importance dans les choix des collectivités territoriales de la prise en compte des caractéristiques des usagers, une politique étant d’autant plus efficace que les usagers du service sont prêts à la mettre en oeuvre.D’autre part, à partir d’une approche en sciences humaines et sociales, nous constatons une relation entre l’usager et le service de gestion des déchets assez complexe, ainsi que des pratiques de tri bien ancrées dans le quotidien des individus.This research aims at studying the actions developed by local authorities in order to lead households to adopt pro-environmental behaviours. Our research combines two complementary approaches.On the one hand, based on an economic approach, we analyze which choices make local authorities in order to encourage users of waste disposing services to throw away less waste. Within this framework we have established a typology of levers developed by local authorities. Then, based on an econometric study, we have pointed out the importance for local governments of taking into account households’ characteristics in the definition of their waste management strategy.On the other hand, based on a human and social sciences approach, we notice a complex relationship between users and waste management service, as well as sorting practices tightly embedded in individuals’ everyday life

Gestion des déchets ménagers : comment les collectivités françaises mobilisent-elles leurs usagers ?

This research aims at studying the actions developed by local authorities in order to lead households to adopt pro-environmental behaviours. Our research combines two complementary approaches. On the one hand, based on an economic approach, we analyze which choices make local authorities in order to encourage users of waste disposing services to throw away less waste. Within this framework we have established a typology of levers developed by local authorities. Then, based on an econometric study, we have pointed out the importance for local governments of taking into account households’ characteristics in the definition of their waste management strategy.On the other hand, based on a human and social sciences approach, we notice a complex relationship between users and waste management service, as well as sorting practices tightly embedded in individuals’ everyday life.

Modeling the Longitudinal Effects of Insight on Depression, Quality of Life and Suicidality in Schizophrenia Spectrum Disorders: Results from the FACE-SZ Cohort

International audienceBackground: Up to half of the patients with schizophrenia attempt suicide during their lifetime. Better insight is associated with better functioning but also with increased suicidality. The direction of the relationship between insight and suicidality is not clear, hence we aimed to provide new elements using structural equation modeling. Methods: Insight, quality of life (QoL), depression, and suicidality were measured at baseline and at 12 months in individuals with schizophrenia spectrum disorders. The relationships between these variables were investigated by latent difference score models, controlling for chlorpromazine doses, positive and negative symptoms, and general psychopathology. Results: 738 patients were included, and 370 completed the study. Baseline levels of insight predicted changes in suicidality, whereas baseline levels of suicidality did not predict changes in insight, suggesting that better insight underlies suicidality and predicts its worsening. Our results suggest this temporal sequence: better insight → worse QoL → increased depression → increased suicidality, while insight also affects the three variables in parallel. Conclusion: Better insight predicts a worsening of QoL, depression and suicidality. These findings contribute to our global understanding of the longitudinal influence of insight on suicidality. We advocate that insight-targeted interventions should not be proposed without the monitoring of depression and suicide prevention

The puzzle of quality of life in schizophrenia: putting the pieces together with the FACE-SZ cohort

International audienceBackground The determinants of quality of life (QoL) in schizophrenia are largely debated, mainly due to methodological discrepancies and divergence about the concepts concerned. As most studies have investigated bi- or tri-variate models, a multivariate model accounting for simultaneous potential mediations is necessary to have a comprehensive view of the determinants of QOL. We sought to estimate the associations between cognitive reserve, cognition, functioning, insight, depression, schizophrenic symptoms, and QoL in schizophrenia and their potential mediation relationships. Methods We used structural equation modeling with mediation analyses to test a model based on existing literature in a sample of 776 patients with schizophrenia from the FondaMental Foundation FACE-SZ cohort. Results Our model showed a good fit to the data. We found better functioning to be positively associated with a better QoL, whereas better cognition, better insight, higher levels of depression, and schizophrenic symptoms were associated with a lower QoL in our sample. Cognitive reserve is not directly linked to QoL, but indirectly in a negative manner via cognition. We confirm the negative relationship between cognition and subjective QoL which was previously evidenced by other studies; moreover, this relationship seems to be robust as it survived in our multivariate model. It was not explained by insight as some suggested, thus the mechanism at stake remains to be explained. Conclusion The pathways to subjective QoL in schizophrenia are complex and the determinants largely influence each other. Longitudinal studies are warranted to confirm these cross-sectional findings

Visualization of multiple alignments, phylogenies and gene family evolution

International audienceSoftware for visualizing sequence alignments and trees are essential tools for life scientists. In this review, we describe the major features and capabilities of a selection of stand-alone and web-based applications useful when investigating the function and evolution of a gene family. These range from simple viewers, to systems that provide sophisticated editing and analysis functions. We conclude with a discussion of the challenges that these tools now face due to the flood of next generation sequence data and the increasingly complex network of bioinformatics information sources