Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle

The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules

Three-dimensional HepaRG spheroids as a liver model to study human genotoxicity in vitro with the single cell gel electrophoresis assay

International audienceMany efforts have been made in the last 30 years to develop more relevant in vitro models to study genotoxic responses of drugs and environmental contaminants. While 2D HepaRG cells are one of the most promising models for liver toxicology, a switch to 3D cultures that integrate both in vivo architecture and cell-cell interactions has occurred to achieve even more predictive models. preliminary studies have indicated that 3D HepaRG cells are suitable for liver toxicity screening. Our study aimed to evaluate the response of HepaRG spheroids exposed to various genotoxic compounds using the single cell gel electrophoresis assay. HepaRG spheroids were used at 10 days after seeding and exposed for 24 and 48 hours to certain selected chemical compounds (methylmethansulfonate (MMS), etoposide, benzo[a]pyrene (B[a]P), cyclophosphamide (CPA), 7,12-dimethylbenz[a]anthracene (DMBA), 2-acetylaminofluorene (2-AAF), 4-nitroquinoline (4-NQO), 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), acrylamide, and 2-4-diaminotoluene (2,4-DAT)). After treatment, the comet assay was performed on single cell suspensions and cytotoxicity was determined by the ATP assay. Comet formation was observed for all compounds except IQ, etoposide and 2,4-DAT. Treatment of spheroids with rifampicin increased CYP3A4 activity, demonstrating the metabolic capacity of HepaRG spheroids. These data on genotoxicity in 3D HepaRG spheroids are promising, but further experiments are required to prove that this model can improve the predictivity of in vitro models to detect human carcinogens

DNA replication determines timing of mitosis by restricting CDK1 and PLK1 activation

To maintain genome stability, cells need to replicate their DNA before dividing. The kinases CDK1 and PLK1 drive mitotic entry and become active when bulk DNA synthesis is completed at the S/G2 transition. Here, we have tested the hypothesis that DNA replication controls activation of mitotic kinases. Using an optimized double-degron system, we find that human cells unable to initiate DNA replication in S-phase promptly activate CDK1 and PLK1 and prematurely enter mitosis. In the presence of DNA replication, inhibition of CHK1 and p38 leads to premature activation of CDK1 and PLK1. While CDK2 activity promotes DNA replication, activation of CDK1 in S-phase induces severe replication stress. We propose that mitotic kinase activation is governed by a CDK2- and DNA replication-dependent feed-forward loop that ensures timely cell division while preserving genome stability. DNA replication thus functions as a break that coordinates cell cycle activities and determines cell cycle duration

Exploitation du conflit entre capteurs pour la gestion d'un système complexe multi-capteurs

Les systèmes complexes intègrent aujourd hui de nombreux capteurs physiques ou logiques qui facilitent la prise de décisions optimales en fonction de l exosystème et de l endosystème. Ces capteurs sont des sources de données, qui délivrent des informations partielles, imprécises et/ou incertaines, partiellement complémentaires et partiellement redondantes. La théorie des fonctions de croyances offre un cadre formel adapté à la représentation de l imprécision et de l incertitude des informations. Cependant, même en modélisant l ignorance et l imprécision des sources, l absence de conflit entre les sources n est toutefois pas garantie.Dans la théorie des fonctions de croyances, le désaccord entre sources est classiquement mesuré en termes de conflit Dempsterien , celui résultant de la combinaison conjonctive des sources, ou de dis-similarité ou distances entre fonctions de croyance. Toutes ces mesures sont globales, et ne donnent pas d information directe sur la source du conflit.La contribution principale de cette thèse est de décomposer le conflit Dempsterien dans le but d'analyser celui-ci. Nous proposons une décomposition par rapport aux différentes hypothèses simples ou composées, issues de l'espace de discernement. Nous montrons l unicité de cette décomposition et explicitons l algorithme de calcul, à partir de la décomposition canonique de la fonction de croyance. Nous interprétons alors chacun des termes de la décomposition comme la contribution au conflit global, apportée par chaque hypothèse simple ou composée. Cette décomposition s applique à l analyse du confit intra-source (i.e. le conflit inhérent à la source) ou du conflit inter-sources (i.e. le conflit qui apparait lors de la fusion des sources). Nous illustrons sur des exemples jouets comment l observation de la répartition du conflit par rapport aux différentes hypothèses peut permettre l identification de l origine de certains conflits. Trois applications de notre mesure sont ensuite développées, afin d illustrer son utilité.La première application concerne la détection préventive de chute un véhicule type bicycle (moto). Les sources de données sont les accélérations mesurées sur les deux roues. Un conflit entre ces mesures, supposées hautement redondantes, voire corrélées, sera alors interprété comme un début de chute. Nous montrons que la décomposition du conflit fournit un indicateur de chute plus fin et précoce que la mesure du conflit Dempsterien.La deuxième application concerne la localisation de véhicule, problème essentiel pour l autonomie des véhicules d'exploration comme des robots de service. Les sources sont des sorties d algorithmes d estimation de mouvement du véhicule. Nous montrons d abord qu estimer dynamiquement la fiabilité des sources permet d améliorer la fusion. Nous montrons ensuite que la décomposition du conflit permet une mesure plus fine de la fiabilité de la fusion que la mesure du conflit Dempsterien. En cas de conflit détecté, l estimation de la fiabilité de chaque source est ensuite fondée sur la vérification (ou non) d une hypothèse de régularité temporelle, vérification elle-même basée sur une mesure de distance locale aux hypothèses simples ou composées. La troisième application propose une généralisation de la combinaison hybride de Dubois Prade au cas de la combinaison à N sources. Notre mesure calculant le conflit partiel associé à chaque sous-ensemble d hypothèses, en nous inspirant du principe de la règle de combinaison hybride, nous redistribuons la masse de ce conflit partiel à la disjonction des hypothèses du sous-ensemble. La décomposition du conflit permet d identifier de manière unique les différents sous-ensembles d hypothèses contribuant au conflit.En conclusion, les travaux ont montré que l information issue de la mesure du conflit, et de sa décomposition, pouvait (devait) être considérée comme une information à part entière, permettant notamment la gestion des sources et des croyances à fusionner.Complex systems are now integrating many sensors, physical or logical, in order to be able to take the best decision knowing the exosystem and endosystem. These sensors are data sources, which deliver partial information, imprecise and/or uncertain, partially complementary and partially redundant. The theory of belief functions is now widely used in data fusion because it provides a formal framework for the representation of both imprecise and uncertainty information. However, even modeling the ignorance and the imprecision of the sources, the source combination usually lets appear some disagreement/conflict between sources.A disagreement between sources makes the system unstable and can impact the decision. Thus, for managing the disagreement, several authors have developed different combination rules where the Dempster's conflict is transferred to a set of elements. A few works have proposed to consider the conflict as a piece of information exploitable beyond the scope of the combination. In this work, we aim at decomposing the Dempster's conflict in order to better interpret it. We propose a decomposition with respect to different assumptions simple or compound of discernment space. We show the uniqueness of this decomposition and we specify the algorithm, based on the canonical decomposition of belief function. We then interpret each term of the decomposition as the contribution, to global conflict, brought by each hypothesis simple or compound. This decomposition is applied to the analysis of intra-conflict source (i.e. the conflict inherent in the source) or inter-conflict sources (i.e. the conflict appearing during the fusion of sources). We illustrate on toy examples how observing the distribution of conflict with respect to different assumptions may allow the identification of the origin of some conflicts.Three applications of our measurement have been developed to illustrate its usefulness.The first application deals with the preventive detection of fall for motorbike. Typical data sources are speed and accelerations measured on each of the two wheels. A conflict between these measures, supposed highly redundant or even correlated, should be interpreted as an early fall (sliding, shock). We show that the decomposition of conflict provides a finer and earlier indicator of fall than Dempster's conflict.The second application is the localization of the vehicle, the key issue being for autonomous exploration vehicles such as service robots. The sources are outputs of algorithms estimating the movement of the vehicle (such as odometers, visual odometry, FastSLAM). We first show that estimating the reliability of sources dynamically improves fusion. We then show that the decomposition of conflict allows a more refined measure of the fusion reliability than Dempster's conflict. Now, when conflict is detected, the estimation of the reliability of each source is based on the verification (or not) of an assumption of temporal regularity, verification itself based on a distance measure local to the discernment space hypotheses.The third application is the generalization of the hybrid combination [Dubois and Prade, 1988] to the case of N sources. Our measure calculates the partial conflicts associated with each subset of hypotheses. Following the hybrid combination [Dubois and Prade, 1988] principle, we redistribute the mass associated to a partial conflict on the disjunction of the hypotheses involving this partial conflict. In this redistribution, our decomposition of the conflict is essential since it allows identifying uniquely the various sub-sets of hypotheses involving partial conflicts.In conclusion, this work has shown that the information derived from the conflict measurement, and its decomposition could (should) be considered a full information, particularly for the management of sources and beliefs to combine.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Estimation du contexte par vision embarquée et schémas de commande pour l'automobile

Les systèmes dotés d autonomie doivent continument évaluer leur environnement, via des capteurs embarqués, afin de prendre des décisions pertinentes au regard de leur mission, mais aussi de l endosystème et de l exosystème. Dans le cas de véhicules dits intelligents , l attention quant au contexte environnant se porte principalement d une part sur des objets parfaitement normalisés, comme la signalisation routière verticale ou horizontale, et d autre part sur des objets difficilement modélisables de par leur nombre et leur variété (piétons, cyclistes, autres véhicules, animaux, ballons, obstacles quelconques sur la chaussée, etc ). La décision a contrario offre un cadre formel, adapté à ce problème de détection d objets variables, car modélisant le bruit plutôt qu énumérant les objets à détecter. La contribution principale de cette thèse est d adapter des mesures probabilistes de type NFA (Nombre de Fausses Alarmes) au problème de la détection d objets soit ayant un mouvement propre, soit saillants par rapport au plan de la route. Un point fort des algorithmes développés est qu ils s affranchissent de tout seuil de détection. Une première mesure NFA permet d identifier le sous-domaine de l'image (pixels non nécessairement connexes) dont les valeurs de niveau de gris sont les plus étonnantes, sous hypothèse de bruit gaussien (modèle naïf). Une seconde mesure NFA permet ensuite d identifier le sous-ensemble des fenêtres de significativité maximale, sous hypothèse de loi binômiale (modèle naïf). Nous montrons que ces mesures NFA peuvent également servir de critères d optimisation de paramètres, qu il s agisse du mouvement 6D de la caméra embarquée, ou d un seuil de binarisation sur les niveaux de gris. Enfin, nous montrons que les algorithmes proposés sont génériques au sens où ils s appliquent à différents types d images en entrée, radiométriques ou de disparité.A l opposé de l approche a contrario, les modèles markoviens permettent d injecter des connaissances a priori sur les objets recherchés. Nous les exploitons dans le cas de la classification de marquages routiers.A partir de l estimation du contexte (signalisation, détection d objets inconnus ), la partie commande comporte premièrement une spécification des trajectoires possibles et deuxièmement des lois en boucle fermée assurant le suivi de la trajectoire sélectionnée. Les diverses trajectoires possibles sont regroupées en un faisceau, soit un ensemble de fonctions du temps où divers paramètres permettent de régler les invariants géométriques locaux (pente, courbure). Ces paramètres seront globalement fonction du contexte extérieur au véhicule (présence de vulnérables, d'obstacles fixes, de limitations de vitesse, etc.) et permettent de déterminer l'élément du faisceau choisi. Le suivi de la trajectoire choisie s'effectue alors en utilisant des techniques de type platitude différentielle, qui s'avèrent particulièrement bien adaptées aux problèmes de suivi de trajectoire. Un système différentiellement plat est en effet entièrement paramétré par ses sorties plates et leurs dérivées. Une autre propriété caractéristique de ce type de systèmes est d'être linéarisable de manière exacte (et donc globale) par bouclage dynamique endogène et transformation de coordonnées. Le suivi stabilisant est alors trivialement obtenu sur le système linéarisé.To take relevant decisions, autonomous systems have to continuously estimate their environment via embedded sensors. In the case of 'intelligent' vehicles, the estimation of the context focuses both on objects perfectly known such as road signs (vertical or horizontal), and on objects unknown or difficult to describe due to their number and variety (pedestrians, cyclists, other vehicles, animals, any obstacles on the road, etc.). Now, the a contrario modelling provides a formal framework adapted to the problem of detection of variable objects, by modeling the noise rather than the objects to detect. Our main contribution in this PhD work was to adapt the probabilistic NFA (Number of False Alarms) measurements to the problem of detection of objects simply defined either as having an own motion, or salient to the road plane. A highlight of the proposed algorithms is that they are free from any detection parameter, in particular threshold. A first NFA criterion allows the identification of the sub-domain of the image (not necessarily connected pixels) whose gray level values are the most amazing under Gaussian noise assumption (naive model). A second NFA criterion allows then identifying the subset of maximum significant windows under binomial hypothesis (naive model). We prove that these measurements (NFA) can also be used for the estimation of intrinsec parameters, for instance either the 6D movement of the onboard camera, or a binarisation threshold. Finally, we prove that the proposed algorithms are generic and can be applied to different kinds of input images, for instance either radiometric images or disparity maps. Conversely to the a contrario approach, the Markov models allow to inject a priori knowledge about the objects sought. We use it in the case of the road marking classification. From the context estimation (road signs, detected objects), the control part includes firstly a specification of the possible trajectories and secondly the laws to achieve the selected path. The possible trajectories are grouped into a bundle, and various parameters are used to set the local geometric invariants (slope, curvature). These parameters depend on the vehicle context (presence of vulnerables, fixed obstacles, speed limits, etc ... ), and allows determining the selected the trajectory from the bundle. Differentially flat system is indeed fully parameterized by its flat outputs and their derivatives. Another feature of this kind of systems is to be accurately linearized by endogenous dynamics feed-back and coordinate transformation. Tracking stabilizer is then trivially obtained from the linearized system.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Effects of Exogenous Application of Osmotic Adjustment Substances on Growth, Pigment Concentration, and Physiological Parameters of Dracaena sanderiana Sander under Different Levels of Salinity

We evaluated two osmotic adjustment substances (glycine betaine (GB) and glycine (G) and a combination of both glycine + glycine betaine (G + GB) using two modes of application; irrigation and foliar sprays with Dracaena sanderiana plants. The plants were grown in containers and subjected to two levels of NaCl concentrations (2.0 and 7.5 dS m−1) over 8 weeks. Growth, pigment concentrations, and physiological parameters were assessed at the end of the trial. The foliar application of GB resulted in most optimal plant growth and biomass production in the presence of NaCl. The chlorophyll and carotenoid concentrations showed different trends depending on the osmotic adjustment substance applied and the mode of application. Stomatal density and dimensions varied considerably with respect to the osmotic adjustment substance supplied. The concentration of soluble sugars in leaves did not show a clear trend under the different treatments assessed. The exogenous application of G resulted in the highest concentration of free proline and proteins in leaves. The antioxidant capacity in leaves increased with both osmotic adjustment substances, and both means of application, under low and high saline conditions. We concluded that the foliar application of GB can be recommended in order to achieve cost-effective growth of D. sanderiana under saline conditions

Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B

Two mitotic cyclin types, cyclin A and B, exist in higher eukaryotes, but their specialised functions in mitosis are incompletely understood. Using degron tags for rapid inducible protein removal, we analyse how acute depletion of these proteins affects mitosis. Loss of cyclin A in G2-phase prevents mitotic entry. Cells lacking cyclin B can enter mitosis and phosphorylate most mitotic proteins, because of parallel PP2A:B55 phosphatase inactivation by Greatwall kinase. The final barrier to mitotic establishment corresponds to nuclear envelope breakdown, which requires a decisive shift in the balance of cyclin-dependent kinase Cdk1 and PP2A:B55 activity. Beyond this point, cyclin B/Cdk1 is essential for phosphorylation of a distinct subset of mitotic Cdk1 substrates that are essential to complete cell division. Our results identify how cyclin A, cyclin B and Greatwall kinase coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phosphorylation

The development of arable cultivation in the south-east of England and its relationship with vegetation cover: A honeymoon period for biodiversity?

The onset of prehistoric farming brought unprecedented changes to landscapes and their biodiversity. Past biodiversity patterns are broadly understood for different parts of Europe, and demonstrate trajectories that have been linked to prehistoric and historic demographic transitions, and associated land-use practices. To our knowledge, this paper is the first attempt to directly link evidence of agricultural practice from the archaeological record to biodiversity patterns. Records of fossil pollen are used to estimate plant and landscape diversity patterns, and novel approaches are employed to analyse 1194 harmonised archaeobotanical samples (plant macrofossil remains) spanning the prehistoric and Roman periods, from southern England. We demonstrate changes in the use of crops and gathered edible plants and non-linear trends in cultivation practices. Whilst, overall, cereal production is characterised by ever larger and extensive regimes, different trajectories are evident for most of early prehistory, the Middle Iron Age and the Late Roman period. Comparisons with the Shannon diversity of fossil pollen records from the same region suggest a positive relationship between developing agricultural regimes and landscape scale biodiversity during the prehistoric period. The Roman period represents a tipping point in the relationship between expanding agriculture and pollen diversity, with declining pollen diversity evident in the records from the region

Evaluation of a Change Detection Methodology by Means of Binary Thresholding Algorithms and Informational Fusion Processes

Landcover is subject to continuous changes on a wide variety of temporal and spatial scales. Those changes produce significant effects in human and natural activities. Maintaining an updated spatial database with the occurred changes allows a better monitoring of the Earth’s resources and management of the environment. Change detection (CD) techniques using images from different sensors, such as satellite imagery, aerial photographs, etc., have proven to be suitable and secure data sources from which updated information can be extracted efficiently, so that changes can also be inventoried and monitored. In this paper, a multisource CD methodology for multiresolution datasets is applied. First, different change indices are processed, then different thresholding algorithms for change/no_change are applied to these indices in order to better estimate the statistical parameters of these categories, finally the indices are integrated into a change detection multisource fusion process, which allows generating a single CD result from several combination of indices. This methodology has been applied to datasets with different spectral and spatial resolution properties. Then, the obtained results are evaluated by means of a quality control analysis, as well as with complementary graphical representations. The suggested methodology has also been proved efficiently for identifying the change detection index with the higher contribution