Éditeur(s) : HAL CCSD
Résumé : International audience
In this work, we present an analysis of a one-year period measured wind speed in the atmospheric boundary layer from a wind energy production site. We employ a Hilbert-based methodology, namely arbitrary-order Hilbert spectral analysis, to characterize the intermittent property of the wind speed in a joint amplitude-frequency space. The measured scaling exponents implies intermittent nature of the wind on mesoscales.
Wind Energy-Impact of turbulence

hal-01528079
https://hal.archives-ouvertes.fr/hal-01528079
DOI : 10.1007/978-3-642-54696-9

Éditeur(s) : HAL CCSD Non-Linéaire Publications
Résumé : Depuis quelques decennies, l'energie eolienne conna^t une croissance considerable. Cependant cette energie est dependante de la vitesse du vent variant en intensite sur des echelles de temps qui incluent l'annee, la journee 'a quelques secondes. L'objectif de ce travail est de caracteriser les uctuations d'une serie temporelle de production eolienne. Dans un premier temps, nous verions l'utilisation de la Loi de Taylor, relation entre l'ecart type 2 P et la moyenne < p > : 2 P = C < p >. Cette relation fut observee en ecologie, en nance, dans les sciences du vivant et pour des donnees de trac internet [1]. De recents travaux fournissent des hypotheses d'explication quant a l'origine de cette loi [2,3]. L'exposant caracterise le type de dynamique du processus considere et varie entre 1=2 et 1. Dans notre cas d'etude, l'estimation de l'exposant est proche de 1. Quand = 1, les processus consideres sont a invariance d'echelle [1]. Pour mettre en evidence les proprietes d'invariance d'echelle de notre serie temporelle, nous eectuons une analyse multifractale pour estimer la fonction exposant d'echelle (h) a l'aide des moments d'ordre h de l'increment temporel des donnees de production eolienne P = P(t + ) P(t), telle que < Pq > (h) [5]. La fonction (h) est concave et non-lineaire : plus elle est concave, plus la serie analysee sera intermittente. Nous montrons que la serie temporelle de la production eolienne consideree est intermittente et possede des proprietes multifractales. De plus le modele de cascades aleatoires log-normal se revele pertinent pour decrire ces fluctuations.
Rencontre du Non-Linéaire

ISBN : 978-2-9538596-1-4
hal-00760932
https://hal.archives-ouvertes.fr/hal-00760932

Éditeur(s) : HAL CCSD European Geosciences Union (EGU)
Résumé : International audience
We consider here wind speed time series and the aggregate output wind power from a wind farm. We study their scaling statistics in the framework of fully developed turbulence and Kolmogorov's theory. We estimate their Fourier power spectra and consider their scaling properties in the physical space. We show that the atmospheric wind speed and the aggregate power output from a wind farm are intermittent and multifractal over a wide range of scales. The coupling between simultaneous data of the wind speed and aggregate power output is investigated through a joint multifractal description using the generalized correlation functions (GCFs). This multiscaling test is compatible with a linear relation between the wind speed and the aggregate power output fluctuations for timescales T > 103 s ' 15min.
ISSN: 1023-5809

hal-00958490
https://hal.archives-ouvertes.fr/hal-00958490
DOI : 10.5194/npg-21-379-2014

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The objectives are to study and model the aggregate wind power fluctuations dynamics in the multifractal framework. We present here the analysis of aggregate power output sampled at 1 Hz during three years. We decompose the data into several Intrinsic Mode Functions (IMFs) using Empirical Mode Decomposition (EMD). We use a new approach, arbitrary order Hilbert spectral analysis, a combination of the EMD approach with Hilbert spectral analysis (or Hilbert-Huang Transform) and the classical structure-function analysis to extract the scaling exponents or multifractal spectrum ζ(q)ζ(q): this function provides a full characterization of a process at all intensities and all scales. The application of both methods, i.e. structure-function and arbitrary-order Hilbert spectral analyses, gives similar results indicating that the aggregate power output from a wind farm, possesses intermittent and multifractal properties. In order to check this result, we generate stochastic simulations of a Multifractal Random Walk (MRW) using a log-normal stochastic equation. We show that the simulation results are fully compatible with the experimental results
Physica A

hal-00846643
https://hal.archives-ouvertes.fr/hal-00846643
DOI : 10.1016/j.physa.2013.04.038

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
A good knowledge of the intermittency of global solar radiation is crucial for selecting the location of a solar power plant and predicting the generation of electricity. This paper presents a multifractal analysis study of 367 daily global solar radiation sequences measured with a sampling rate of 1 Hz over one year at Guadeloupean Archipelago (French West Indies) located at 16°15'N latitude and 60°30'W longitude. The mean power spectrum computed follows a power law behaviour close to the Kolmogorov spectrum. The intermittent and multifractal properties of global solar radiation data are investigated using several methods. Under this basis, a characterization for each day using three multifractal parameters is proposed
ISSN: 0038-092X

hal-01527892
https://hal.archives-ouvertes.fr/hal-01527892
DOI : 10.1016/j.solener.2013.09.018

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Activation of cell signaling by reactive chemicals and pollutants is an important issue for human health. It has been shown that lipophilic nitro-benzoxadiazole (NBD) compounds rapidly move across the plasma membrane and enhance Epidermal Growth Factor Receptor (EGFR) tyrosine phosphorylation in cancer cells. Unlike ligand-dependent activation, the mechanism of this induction relies on the generation of hydrogen peroxide, which is involved in the activation of the catalytic site of the receptor and the inactivation of protein tyrosine phosphatase PTP-1B. Production of H2O2 during redox transformation of NBD compounds is associated with the transition of a monomeric form of Cu/Zn superoxide dismutase 1 (SOD1) to stable dimers. The highly stable and functionally active SOD1 dimer, in the absence of adequate activities in downstream reactions, promotes the disproportionate production and accumulation of intracellular hydrogen peroxide shortly after exposure to NBD compounds. The intrinsic fluorescence of small compounds was used to demonstrate their binding to SOD1. Our data indicate that H2O2 and concomitantly generated electrophilic intermediates behave as independent entities, but all contribute to the biological reactivity of NBD compounds. This study opens a promising path to identify new biomarkers of oxidative/electrophilic stress in the progression of cancer and other diseases
ISSN: 2045-2322

hal-01279094
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01279094
DOI : 10.1038/srep21088
PUBMED : 26883293

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.
ISSN: 2045-2322

hal-01518808
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808/file/Hardonni%C3%A8re%20et%20al%202017.pdf
DOI : 10.1038/s41598-017-00269-7

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We propose a new geometric approach to describe the qualitative dynamics of chemical reactions networks. By this method we identify metastable regimes, defined as low dimensional regions of the phase space close to which the dynamics is much slower compared to the rest of the phase space. These metastable regimes depend on the network topology and on the orders of magnitude of the kinetic parameters. Benchmarking of the method on a computational biology model repository suggests that the number of metastable regimes is sub-exponential in the number of variables and equations. The dynamics of the network can be described as a sequence of jumps from one metastable regime to another. We show that a geometrically computed con-nectivity graph restricts the set of possible jumps. We also provide finite state machine (Markov chain) models for such dynamic changes. Applied to signal transduction models, our approach unravels dynamical and functional * corresponding author capacities of signalling pathways, as well as parameters responsible for speci-ficity of the pathway response. In particular, for a model of TGFβ signalling, we find that the ratio of TGFBR2 to TGFBR1 receptors concentrations can be used to discriminate between metastable regimes. Using expression data from the NCI60 panel of human tumor cell lines, we show that aggressive and non-aggressive tumour cell lines function in different metastable regimes and can be distinguished by measuring the relative concentrations of receptors of the two types.
ISSN: 0303-2647

hal-01379033
https://hal.inria.fr/hal-01379033
https://hal.inria.fr/hal-01379033/document
https://hal.inria.fr/hal-01379033/file/Samal_et_al_Biosystems_final.pdf
DOI : 10.1016/j.biosystems.2016.07.004

Éditeur(s) : HAL CCSD
Résumé : We present an experimental study of relations between hydraulic properties of clayey rocks and their deformation at bulk and micro scale. The experimentation is based on triaxial deformation of kaolinitic core samples, on permeability measurements, and on several methods of analysis of the microstructure. To produce the samples, remoulded kaolinite material is consolidated by axial loading up to 20 MPa in an oedometric cell. Then, in a triaxial cell, an undrained stress path is applied in order to induce shearing damage in the sample. The permeability of the sample is measured by fluid flow across the sample. Before and after these hydro-mechanical tests, the evolution and the homogeneity of the pore space and moreover the texture of the material are analysed by X-ray tomography, environmental scanning electron microscopy and thermic neutron diffraction. Contrary to expectations, the permeability at the sample scale does not vary significantly, although quite large deformation is reached. The final deformation is heterogeneous, with well-developed shear bands. It appears that the development of compacting and dilating zones generates a heterogeneous permeability field, which results in a negligible variation of the bulk permeability at the sample scale.
International Journal of Rock Mechanics and Mining Science

hal-00496407
https://hal.archives-ouvertes.fr/hal-00496407
DOI : 10.1016/j.ijrmms.2010.04.007

Éditeur(s) : HAL CCSD American Association for Cancer Research
Résumé : International audience
Homing of CD8+ T lymphocytes to the tumor microenvironment is an important step for mounting a robust antitumor immune response. TGF-β is responsible for CD103 (αEβ7) integrin induction in activated intraepithelial CD8+ T lymphocytes. However, the interplay between TGF-β and CD103 and their contribution to T-cell infiltration and antitumor activity remain unknown. Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Moreover, TGF-β enhanced CD103-dependent T-cell adhesion and signaling, whereas it inhibited leukocyte function-associated antigen (LFA)-1 (αLβ2) integrin expression and LFA-1-mediated T-lymphocyte functions. Mechanistic investigations revealed that TGF-β bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrin-linked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation thereby initiating integrin inside-out signaling. Collectively, our findings suggest that the abundance of TGF-β in the tumor microenvironment may in fact engage with integrin signaling pathways to promote T-lymphocyte antitumor functions, with potential implications for T-cell-based immunotherapies for cancer
ISSN: 0008-5472

Droits : info:eu-repo/semantics/OpenAccess
hal-01282442
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442/file/TGF%CE%B2%20Signaling%20Intersects%20with%20CD103-boutet2016-final.pdf
DOI : 10.1158/0008-5472.CAN-15-1545

Éditeur(s) : HAL CCSD Impact journals
Résumé : International audience
TNF-Related Apoptosis-Inducing Ligand (TRAIL) is a well-known apoptosis inducer, which activates the extrinsic death pathway. TRAIL is pro-apoptotic on colon cancer cells, while not cytotoxic towards normal healthy cells. However, its clinical use is limited by cell resistance to cell death which occurs in approximately 50% of cancer cells. Short Chain Fatty Acids (SCFA) are also known to specifically induce apoptosis of cancer cells. In accordance, we have shown that food grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via the production and release of SCFA (propionate and acetate) acting on mitochondria. Here, we investigated possible synergistic effect between Propionibacterium freudenreichii and TRAIL. Indeed, we hypothesized that acting on both extrinsic and intrinsic death pathways may exert a synergistic pro-apoptotic effect. Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial metabolites (propionate and acetate), in combination with TRAIL, increased pro-apoptotic gene expression (TRAIL-R2/DR5) and decreased anti-apoptotic gene expression (FLIP, XIAP) in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on both death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and caspases (caspase-8, -9 and -3) activation, was lethal on cancer cells but not on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented by P. freudenreichii induced HT29 cells apoptosis and enhanced TRAIL cytotoxic activity, as did P. freudenreichii DMEM culture supernatants or its SCFA metabolites. These results open new perspectives for food grade P. freudenreichii-containing products in order to potentiate TRAIL-based cancer therapy in colorectal cancer
ISSN: 1949-2553

hal-01259215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259215
DOI : 10.18632/oncotarget.6881
PUBMED : 26771233

Éditeur(s) : HAL CCSD
Journées Ouvertes en Biologie, Informatique et Mathématiques (JOBIM)
Rennes, France

hal-00760183
https://hal.inria.fr/hal-00760183

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 1476-9271

hal-01401685
https://hal.inria.fr/hal-01401685
DOI : 10.1016/j.compbiolchem.2016.01.012
PUBMED : 26878129

Éditeur(s) : HAL CCSD
Résumé : International audience
ISMB 2012
Long Beach, United States

hal-00760189
https://hal.inria.fr/hal-00760189

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In this paper, we have presented a spectral and a multifractal analysis performed on 412 time series of wind speed data each of duration of 350 s and sampled at 20 Hz. The average spectrum for the wind speed displays a scaling behavior, in the inertial range, over two decades, with β=1.68 close to the Kolmogorov value −5/3. A multifractal analysis has been motivated by the presence of scaling invariance in data set. Then we have considered their scaling properties in the framework of fully developed turbulence and multifractal cascades. The results obtained for wind speed confirm that the exponent scaling function ζV(q) is nonlinear and concave. This exponent characterizes the scaling functions in the inertial range indicating that the wind speed is intermittent and multifractal. Moreover the theoretical quadratic relation for lognormal multifractals is well fitted. We investigate the consequence for wind energy production: we generate stochastic simulations of a multifractal random walk, and using a power curve derived from experimental data, we generate the associated power time series. We show that, due to the saturation of the power curve for large speed values, when the input time series (turbulent wind speed) is multifractal, the output can be almost monofractal.
ISSN: 0167-6105

hal-00779049
https://hal.archives-ouvertes.fr/hal-00779049
DOI : 10.1016/j.jweia.2012.06.002

Éditeur(s) : HAL CCSD
Résumé : International audience
The study of complex biological processes requires to forgo simplified models for extensive ones. Yet, these models' size and complexity place them beyond understanding. Their analysis requires new methods for identifying general patterns. The Transforming Growth Factor TGF-β is a multifunctional cytokine that regulates mammalian cell development , differentiation, and homeostasis. Depending on the context, it can play the antagonistic roles of growth inhibitor or of tumor promoter. Its context-dependent pleiotropic nature is associated with complex sig-naling pathways. The most comprehensive model of TGF-β-dependent signaling is composed of 15,934 chains of reactions (trajectories) linking TGF-β to at least one of its 159 target genes. Identifying functional patterns in such a network requires new automated methods. This article presents a framework for identifying groups of similar trajec-tories composed of the same molecules using an exhaustive and without prior assumptions approach. First, the trajectories were clustered using the Relevant Set Correlation model, a shared nearest-neighbors clustering method. Five groups of trajectories were identified. Second, for each cluster the over-represented molecules were determined by scoring the frequency of each molecule implicated in trajectories. Third, Gene set enrichment analysis on the clusters of trajectories revealed some specific TGF-β-dependent biological processes, with different clusters associated to the antagonists roles of TGF-β. This confirms that our approach yields biologically-relevant results. We developed a web interface that facilitates graph visualization and analysis. Our clustering-based method is suitable for identifying families of functionally-similar trajectories in the TGF-β signaling network. It can be generalized to explore any large-scale biological pathways.
CMSB 2017 - 15th International Conference on Computational Methods in Systems Biology
Darmstadt, France

hal-01559249
https://hal.archives-ouvertes.fr/hal-01559249
https://hal.archives-ouvertes.fr/hal-01559249/document
https://hal.archives-ouvertes.fr/hal-01559249/file/JeanCoquet_CMSB.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
An exploration 3D seismic data set from the Gjallar Ridge off mid-Norway images a giant fluid seep structure 3 × 5 km wide, which connects to late Palaeocene magmatic sills at depth. Two of the pipes that have developed as hydrothermal vents reach all the way to the modern seafloor implying that they either were active much longer than the original hydrothermal activity or have been reactivated. We combine detailed seismic analysis of the northern pipe and sandbox modeling to constrain pipe initiation and propagation. Although both the seismic data and the sandbox models suggest that fluids at depth are focused through a vertical conduit, sandbox models show that fluids ascend and reach a critical depth migration where focused migration abruptly transforms into distributed fluid flow through unconsolidated sediments. This indicates that at this level the sediments are intensely deformed during pipe propagation, creating a V-shaped structure, i.e. an inverted cone at depth and a positive relief anomaly, 5 to 10 m high, at the seafloor, which is clearly identified on 3D seismic data. Comparison of the geometries observed in sandbox modeling with the seismically observed geometries of the Giant Gjallar Vent suggests that the Giant Gjallar Vent may be a proto-fluid seep at an early stage of its development, preceding the future collapse of the structure forming a seafloor depression. Our results imply that the Gjallar Giant Vent can be used as a window into the geological processes active in the deep parts of the Vøring Basin.
ISSN: 0025-3227

hal-00772465
https://hal.archives-ouvertes.fr/hal-00772465
DOI : 10.1016/j.margeo.2012.08.010

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The Southwest Indian Ocean (SWIO) is a striking marine biodiversity hotspot. Coral reefs in this region host a high proportion of endemics compared to total species richness and they are particularly threatened by human activities. The island archipelagos with their diverse marine habitats constitute a natural laboratory for studying diversification processes. Rocky shores in the SWIO region have remained understudied. This habitat presents a high diversity of molluscs, in particular gastropods. To explore the role of climatic and geological factors in lineage diversification within the genus Nerita, we constructed a new phylogeny with an associated chronogram from two mitochondrial genes [cytochrome oxidase sub-unit 1 and 16S rRNA], combining previously published and new data from eight species sampled throughout the region. All species from the SWIO originated less than 20 Ma ago, their closest extant relatives living in the Indo-Australian Archipelago (IAA). Furthermore, the SWIO clades within species with Indo-Pacific distribution ranges are quite recent, less than 5 Ma. These results suggest that the regional diversification of Nerita is closely linked to tectonic events in the SWIO region. The Reunion mantle plume head reached Earth's surface 67 Ma and has been stable and active since then, generating island archipelagos, some of which are partly below sea level today. Since the Miocene, sea-level fluctuations have intermittently created new rocky shore habitats. These represent ephemeral stepping-stones, which have likely facilitated repeated colonization by intertidal gastropods, like Nerita populations from the IAA, leading to allopatric speciation. This highlights the importance of taking into account past climatic and geological factors when studying diversification of highly dispersive tropical marine species. It also underlines the unique history of the marine biodiversity of the SWIO region.
ISSN: 1932-6203

hal-01185713
https://hal.archives-ouvertes.fr/hal-01185713
https://hal.archives-ouvertes.fr/hal-01185713/document
https://hal.archives-ouvertes.fr/hal-01185713/file/PLoS%20ONE%202014%20Postaire.pdf
DOI : 10.1371/journal.pone.0095040

Éditeur(s) : HAL CCSD
Résumé : Cell signaling contains the whole biological mecanisms allowing the response of a cell to its microenvironnement in an adapted way. Many extremely intertwinned biological reactions are involved in a network that behaves as a complex system. The understanding of cell response requires the development of data acquisition technics and methods to formalize data into models. This point is the main drive of this thesis. We present here two approaches in order to analyse different granularities of cell signaling. In the first one, we used differential model to study the role of a new component of TGF-β canonical pathway. In the second one, we explored the combinatorial complexity of cell signaling, developing a discrete formalism based on guarded transitions. In this approach, we interpreted the whole database Pathway Interaction Database into a single unified model of signal transduction. Simulation and analysis methods, such as reachability and invariance research, have been developed. The interests are presented through an application on cell cycle regulation by cell signaling, and a global analysis on the regulation of genes compared to experimental data.
La signalisation cellulaire regroupe l'ensemble des mécanismes biologiques permettant à une cellule de répondre de façon adaptée à son microenvironnement. Pour ce faire, de nombreuses réactions biologiques entrent en jeux avec un important enchevêtrement, créant ainsi un réseau dont le comportement s'apparente à un système complexe. Le compréhension de la réponse cellulaire à une stimulation passe par le développement conjoint des techniques d'acquisition de données, et des méthodes permettant de formaliser ces données dans un modèle. C'est sur ce dernier point que s'inscrivent les travaux exposés dans cette thèse. Nous présentons ici deux approches visant à répondre à des questions de natures différentes sur la signalisation cellulaire. Dans la première nous utilisons un modèle différentiel pour étudier le rôle d'un nouvel interactant dans la voie canonique du TGF-beta. Dans la seconde nous avons exploré la combinatoire de la signalisation cellulaire en développant un formalisme discret basé sur les transitions gardées. Cette approche regroupe l'interprétation de la base de données Pathway Interaction Database dans un unique modèle dynamique de propagation du signal. Des méthodes de simulations et d'analyses inspirées des techniques de vérification de modèles telles que l'atteignabilité et l'invariance ont été développées. En outre, nous avons étudié la régulation du cycle cellulaire en réponse à la signalisation, ainsi que la régulation des gènes de notre modèle en comparaison avec des données d'expressions.
https://tel.archives-ouvertes.fr/tel-00926487

Droits : info:eu-repo/semantics/OpenAccess
tel-00926487
https://tel.archives-ouvertes.fr/tel-00926487
https://tel.archives-ouvertes.fr/tel-00926487/document
https://tel.archives-ouvertes.fr/tel-00926487/file/AndrieuxThese.pdf

Éditeur(s) : HAL CCSD PeerJ
Résumé : International audience
Background: Heterocyclic aromatic amines (HAA) are environmental and food contaminants that are potentially carcinogenic for humans. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is one of the most abundant HAA formed in cooked meat. MeIQx is metabolized by cytochrome P450 1A2 in the human liver into detoxificated and bioactivated products. Once bioactivated, MeIQx metabolites can lead to DNA adduct formation responsible for further genome instability.Methods: Using a computational approach, we developed a numerical model for MeIQx metabolism in the liver that predicts the MeIQx biotransformation into detoxification or bioactivation pathways according to the concentration of MeIQx.Results: Our results demonstrate that 1) the detoxification pathway predominates, 2) the ratio between detoxification and bioactivation pathways is not linear and shows a maximum at 10µM of MeIQx in hepatocyte cell models, 3) CYP1A2 is a key enzyme in the system that regulates the balance between bioactivation and detoxification. Our analysis suggests that such a ratio could be considered as an indicator of MeIQx genotoxicity at a low concentration of MeIQx.Conclusions: Our model permits the investigation of the balance between bioactivation (i.e. DNA adduct formation pathway through the prediction of potential genotoxic compounds) and detoxification of MeIQx in order to predict the behaviour of this environmental contaminant in the human liver. It highlights the importance of complex regulations of enzyme competitions that should be taken into account in any further multi-organ models.
ISSN: 2167-8359

hal-01575579
https://hal.inria.fr/hal-01575579
PUBMED : 28879062
DOI : 10.7717/peerj.3703