L008 Défaut de différenciation veino-lymphatique embyonnaire par modulation de l’ARN interférence

L’ARN interférence, mécanisme de régulation de l’expression des gènes, est médiée par les siARNs et les microARNs, ARN non-codants de 20 à 22 nucléotides affectant la régulation post-transcriptionnelle d’ARNm cibles avec lesquels ils s’apparient.La RNase DICER est une enzyme centrale de la biosynthèse des siARNs et microARNs. Les souris dont le gène dicer est invalidé ont un phénotype complexe, et meurent très tôt pendant le développement, notamment à cause d’un défaut d’angiogenèse.Afin d’étudier l’ARN interférence au cours de l’angiogenèse embryonnaire, des souris dont le gène dicer est floxé (mutant conditionnel) sont croisées avec des souris exprimant la recombinase Cre, de manière constitutive, sous le contrôle du promoteur du gène tie2, dirigeant ainsi son expression dans les cellules endothéliales (CE) et les cellules hématopiétiques.Nos résultats montrent que l’invalidation de dicer sous le contrôle du promoteur du gène tie2 entraine une mortalité embryonnaire suite à un œdème et des hémorragies au treizième jour du développement (E13,5). L’analyse histologique montre des vaisseaux lymphatiques remplis de sang, suggérant une mauvaise séparation du réseau sanguin et lymphatique. Cette hypothèse est étudiée par marquage des vaisseaux lymphatiques (LYVE-1) et des vaisseaux sanguins (PECAM) sur embryon entier et peaux isolées à différents stades précédant la mort.Ces embryons présentent également un problème de développement du foie, probablement dû à l’activité du promoteur tie2 dans les lignées hématopoiétiques. La mise en culture de ces foies fœtaux à E13,5 révèle une atteinte des précurseurs hématopoétiques.L’étude de ces précurseurs à des stades plus précoces (E8,5) est en cours au laboratoire.Nos résultats démontrent donc un rôle important de l’ARN interférence dans le contrôle épigénétique de l’angiogenèse et de la lymphangiogenèse embryonnaire mais également dans le développement de l’hématopoièse, suggérant son implication dans la différenciation veino-lymphangiogenèse, dont les mécanismes moléculaires seront discutés

Observability and optimal maneuver for bearings only tracking

The aim of this paper is to definite a criteria of quality of the estimates for bearings only tracking . The index of performance is a function of the "condition number" of the error covariance matrix in the extended Kalman filter in the second part, we describe the on-line maneuver of the own ship minimizing the error of the estimâtes . To improve the robustness of the filter a new adaptative algorithm is proposed .Le but de cet article est d'une part de définir un critère qualifiant en temps réel les performances de la poursuite azimétrique en précisant la direction la plus et la moins observable, et d'autre part, de rechercher la manceuvre optimale du lanceur assurant la meilleure observabilité des estimés . Pour améliorer la robustesse du filtre, un algorithme adaptatif est décrit dans la dernière partie de cet article

An advanced Bayesian model for the visual tracking of multiple interacting objects

Visual tracking of multiple objects is a key component of many visual-based systems. While there are reliable algorithms for tracking a single object in constrained scenarios, the object tracking is still a challenge in uncontrolled situations involving multiple interacting objects that have a complex dynamics. In this article, a novel Bayesian model for tracking multiple interacting objects in unrestricted situations is proposed. This is accomplished by means of an advanced object dynamic model that predicts possible interactive behaviors, which in turn depend on the inference of potential events of object occlusion. The proposed tracking model can also handle false and missing detections that are typical from visual object detectors operating in uncontrolled scenarios. On the other hand, a Rao-Blackwellization technique has been used to improve the accuracy of the estimated object trajectories, which is a fundamental aspect in the tracking of multiple objects due to its high dimensionality. Excellent results have been obtained using a publicly available database, proving the efficiency of the proposed approach

Benford's law predicted digit distribution of aggregated income taxes: the surprising conformity of Italian cities and regions

The yearly aggregated tax income data of all, more than 8000, Italian municipalities are analyzed for a period of five years, from 2007 to 2011, to search for conformity or not with Benford's law, a counter-intuitive phenomenon observed in large tabulated data where the occurrence of numbers having smaller initial digits is more favored than those with larger digits. This is done in anticipation that large deviations from Benford's law will be found in view of tax evasion supposedly being widespread across Italy. Contrary to expectations, we show that the overall tax income data for all these years is in excellent agreement with Benford's law. Furthermore, we also analyze the data of Calabria, Campania and Sicily, the three Italian regions known for strong presence of mafia, to see if there are any marked deviations from Benford's law. Again, we find that all yearly data sets for Calabria and Sicily agree with Benford's law whereas only the 2007 and 2008 yearly data show departures from the law for Campania. These results are again surprising in view of underground and illegal nature of economic activities of mafia which significantly contribute to tax evasion. Some hypothesis for the found conformity is presented.Comment: 18 pages, 5 tables, 4 figures, 61 references, To appear in European Physical Journal

In vitro and in vivo characterization of highly purified Human Mesothelioma derived cells

<p>Abstract</p> <p>Background</p> <p>Malignant pleural mesothelioma is a rare disease known to be resistant to conventional therapies. A better understanding of mesothelioma biology may provide the rationale for new therapeutic strategies. In this regard, tumor cell lines development has been an important tool to study the biological properties of many tumors. However all the cell lines established so far were grown in medium containing at least 10% serum, and it has been shown that primary cell lines cultured under these conditions lose their ability to differentiate, acquire gene expression profiles that differ from that of tissue specific stem cells or the primary tumor they derive from, and in some cases are neither clonogenic nor tumorigenic. Our work was aimed to establish from fresh human pleural mesothelioma samples cell cultures maintaining tumorigenic properties.</p> <p>Methods</p> <p>The primary cell cultures, obtained from four human pleural mesotheliomas, were expanded in vitro in a low serum proliferation-permissive medium and the expression of different markers as well as the tumorigenicity in immunodeficient mice was evaluated.</p> <p>Results</p> <p>The established mesothelioma cell cultures are able to engraft, after pseudo orthotopic intraperitoneal transplantation, in immunodeficient mouse and maintain this ability to after serial transplantation. Our cell cultures were strongly positive for CD46, CD47, CD56 and CD63 and were also strongly positive for some markers never described before in mesothelioma cell lines, including CD55, CD90 and CD99. By real time PCR we found that our cell lines expressed high mRNA levels of typical mesothelioma markers as mesothelin (MSLN) and calretinin (CALB2), and of BMI-1, a stemness marker, and DKK1, a potent Wingless [WNT] inhibitor.</p> <p>Conclusions</p> <p>These cell cultures may provide a valuable in vitro and in vivo model to investigate mesothelioma biology. The identification of new mesothelioma markers may be useful for diagnosis and/or prognosis of this neoplasia as well as for isolation of mesothelioma tumor initiating cells.</p

HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development.

Formation of the lymphatic system requires the coordinated expression of several key regulators: vascular endothelial growth factor C (VEGFC), its receptor FLT4, and a key transcriptional effector, PROX1. Yet, how expression of these signaling components is regulated remains poorly understood. Here, using a combination of genetic and molecular approaches, we identify the transcription factor hematopoietically expressed homeobox (HHEX) as an upstream regulator of VEGFC, FLT4, and PROX1 during angiogenic sprouting and lymphatic formation in vertebrates. By analyzing zebrafish mutants, we found that hhex is necessary for sprouting angiogenesis from the posterior cardinal vein, a process required for lymphangiogenesis. Furthermore, studies of mammalian HHEX using tissue-specific genetic deletions in mouse and knockdowns in cultured human endothelial cells reveal its highly conserved function during vascular and lymphatic development. Our findings that HHEX is essential for the regulation of the VEGFC/FLT4/PROX1 axis provide insights into the molecular regulation of lymphangiogenesis