Mapping enzyme-substrate interactions: its potential to study the mechanism of enzymes

With the increase of the need to use more sustainable processes for the industry in our society, the modeling of enzymes has become crucial to fully comprehend their mechanism of action and use this knowledge to enhance and design their properties. A lot of methods to study enzymes computationally exist and they have been classified on sequence-based, structure-based, and the more new artificial intelligence-based ones. Albeit the abundance of methods to help predict the function of an enzyme, molecular modeling is crucial when trying to understand the enzyme mechanism, as they aim to correlate atomistic information with experimental data. Among them, methods that simulate the system dynamics at a molecular mechanics level of theory (classical force fields) have shown to offer a comprehensive study. In this book chapter, we will analyze these techniques, emphasizing the importance of precise modeling of enzyme-substrate interactions. In the end, a brief explanation of the transference of the information from research studies to the industry is given accompanied with two examples of family enzymes where their modeling has helped their exploitation.Peer ReviewedObjectius de Desenvolupament Sostenible::9 - Indústria, Innovació i InfraestructuraPostprint (author's final draft

Integrated monitoring of mola mola behaviour in space and time

Over the last decade, ocean sunfish movements have been monitored worldwide using various satellite tracking methods. This study reports the near-real time monitoring of finescale (< 10 m) behaviour of sunfish. The study was conducted in southern Portugal in May 2014 and involved satellite tags and underwater and surface robotic vehicles to measure both the movements and the contextual environment of the fish. A total of four individuals were tracked using custom-made GPS satellite tags providing geolocation estimates of fine-scale resolution. These accurate positions further informed sunfish areas of restricted search (ARS), which were directly correlated to steep thermal frontal zones. Simultaneously, and for two different occasions, an Autonomous Underwater Vehicle (AUV) videorecorded the path of the tracked fish and detected buoyant particles in the water column. Importantly, the densities of these particles were also directly correlated to steep thermal gradients. Thus, both sunfish foraging behaviour (ARS) and possibly prey densities, were found to be influenced by analogous environmental conditions. In addition, the dynamic structure of the water transited by the tracked individuals was described by a Lagrangian modelling approach. The model informed the distribution of zooplankton in the region, both horizontally and in the water column, and the resultant simulated densities positively correlated with sunfish ARS behaviour estimator (r(s) = 0.184, p < 0.001). The model also revealed that tracked fish opportunistically displace with respect to subsurface current flow. Thus, we show how physical forcing and current structure provide a rationale for a predator's finescale behaviour observed over a two weeks in May 2014

Non-cell autonomous OTX2 transcription factor regulates anxiety-related behaviors in the mouse

The Otx2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, a mesencephalic nucleus involved in the control of complex behaviors through its projections to limbic structures, including the ventral hippocampus, amygdala, nucleus accumbens and prefrontal cortex. We find adult mice heterozygous for Otx2 show a hypoanxious phenotype in light-dark box and elevated plus maze paradigms. However, the number of dopaminergic neurons, the integrity of their axons, their projection patterns in target structures, and the amounts of dopamine and dopamine metabolites in targets structures were not modified in the Otx2 mutant. Because OTX2 is expressed by the choroid plexus, secreted into cerebrospinal fluid and transferred to parvalbumin interneurons of the cortex, hippocampus, and amygdala, we investigated if the hypoanxiety of Otx2 heterozygous mice could result from the decreased synthesis of Otx2 in the choroid plexus. Indeed, hypoanxious phenotype was reversed by the overexpression of Otx2 specifically in choroid plexus of adult Otx2 heterozygous mice, while hypoanxious phenotype could be induced in adult wild type mice by lowering OTX2 levels in the cerebrospinal fluid. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of the anxiety phenotype in the mouse. All rights reserved. No reuse allowed without permission

Role of Syndecans in Ovarian Cancer: New Diagnostic and Prognostic Biomarkers and Potential Therapeutic Targets

Ovarian cancer (OC) is the eighth cancer both in prevalence and mortality in women and represents the deadliest female reproductive cancer. Due to generally vague symptoms, OC is frequently diagnosed only at a late and advanced stage, resulting in high mortality. The tumor extracellular matrix and cellular matrix receptors play a key role in the pathogenesis of tumor progression. Syndecans are a family of four transmembrane heparan sulfate proteoglycans (PG), including syndecan-1, -2, -3, and -4, which are dysregulated in a myriad of cancers, including OC. Many clinicopathological studies suggest that these proteins are promising diagnostic and prognostic biomarkers for OC. Furthermore, functions of the syndecan family in the regulation of cellular processes make it an interesting pharmacological target for anticancer therapies

Influence of the surrounding landscape on the colonization rate of cereal aphids and phytovirus transmission in autumn

International audienceEcological control has often focused on factorsenhancing control of pests by their natural enemies, whilefactors reducing the colonization rate of crops by pestshave been comparatively neglected. We present anapproach to assess landscape influence on the intensity ofwheat colonization by a major crop pest, the aphidRhopalosiphum padi. We used trays containing wheatseedlings to monitor field colonization by R. padi andbarley yellow dwarf viruses’ transmission in two areas inFrance in autumn. We assessed the influence of landscapecomponents likely affecting aphid colonization, i.e. maizeand grasslands as source of migrants on the number ofaphids landing per tray, as well as the host plant of originand the viruliferous potential of migrants. During the survey,maize was the main source of migrants. Virus transmissionwas detected in a few cases (4 % positive assays).Colonization was increased by the presence of maize, butreduced by the presence of grasslands at the landscapescale considered here (i.e. at a radius of 1000 m). Our studycontributes to a better understanding of disease dynamicsin agricultural landscapes. By identifying features of thelandscape that surrounds fields and affects these dynamics,growers can develop more efficient crop protection strategiesrelying on habitat manipulation and rational use ofpesticides

Non-cell autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse

International audienceThe OTX2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, which projects to limbic structures controlling complex behaviors. OTX2 is also produced in choroid plexus epithelium, from which it is secreted into cerebrospinal fluid and transferred to limbic structure parvalbumin interneurons. Previously, adult male mice subjected to early-life stress were found susceptible to anxiety-like behaviors, with accompanying OTX2 expression changes in ventral tegmental area or choroid plexus. Here, we investigated the consequences of reduced OTX2 levels in Otx2 heterozygote mice, as well as in Otx2 +/AA and scFvOtx2 tg/0 mouse models for decreasing OTX2 transfer from choroid plexus to parvalbumin interneurons. Both male and female adult mice show anxiolysis-like phenotypes in all three models. In Otx2 heterozygote mice, we observed no changes in dopaminergic neuron numbers and morphology in ventral tegmental area, nor in their metabolic output and projections to target structures. However, we found reduced expression of parvalbumin in medial prefrontal cortex, which could be rescued in part by adult overexpression of Otx2 specifically in choroid plexus, resulting in increased anxiety-like behavior. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of anxiety phenotypes in the mouse

Le Monte Revincu (Santo-Pietro-di-Tenda, Haute-Corse) : une communauté villageoise de la fin du Ve millénaire av. J. C. au cœur des échanges lithiques en Méditerranée occidentale

Actes du Colloque “La Corse et le monde méditerranéen des origines au Moyen-âge : échanges et circuits commerciaux” Bastia (France), 21-22 novembre 2013.International audienc

Erratum to Establishing constraints on groundwater ages with 36Cl, 14C, 3H, and noble gases: A case study in the eastern Paris basin, France [Applied Geochemistry, 25, 1, (2010), 123-142]

cited By 0International audienceno abstrac