Direct In Vivo Cell Lineage Analysis in the Retrorsine and 2AAF Models of Liver Injury after Genetic Labeling in Adult and Newborn Rats

BACKGROUNDS AND AIMS:When hepatocyte proliferation is impaired, liver regeneration proceeds from the division of non parenchymal hepatocyte progenitors. Oval cells and Small Hepatocyte-like Progenitor Cells (SHPCs) represent the two most studied examples of such epithelial cells with putative stem cell capacity. In the present study we wished to compare the origin of SHPCs proliferating after retrorsine administration to the one of oval cells observed after 2-Acetyl-Amino fluorene (2-AAF) treatment. METHODOLOGY/PRINCIPAL FINDINGS:We used retroviral-mediated nlslacZ genetic labeling of dividing cells to study the fate of cells in the liver. Labeling was performed either in adult rats before treatment or in newborn animals. Labeled cells were identified and characterised by immunohistochemistry. In adult-labeled animals, labeling was restricted to mature hepatocytes. Retrorsine treatment did not modify the overall number of labeled cells in the liver whereas after 2-AAF administration unlabeled oval cells were recorded and the total number of labeled cells decreased significantly. When labeling was performed in newborn rats, results after retrorsine administration were identical to those obtained in adult-labeled rats. In contrast, in the 2-AAF regimen numerous labeled oval cells were present and were able to generate new labeled hepatocytes. Furthermore, we also observed labeled biliary tracts in 2-AAF treated rats. CONCLUSIONS:Our results strongly suggest that SHPCs are derived from hepatocytes and we confirm that SHPCs and oval cells do not share the same origin. We also show that hepatic progenitors are labeled in newborn rats suggesting future directions for in vivo lineage studies

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS

Teaching foreign languages in vocational education in Germany, Catalonia and France : status, uses and representations

Cette thèse explore et compare des représentations élaborées au sujet des langues étrangères ayant leur place dans les curricula de la formation professionnelle du second degré de trois entités socio-historiques et politiques, l’Allemagne, la Catalogne et la France. Elle s’intéresse aussi aux finalités de l’enseignement de ces langues étrangères et aux éventuelles influences exercées par les contextes politiques, idéologiques, sociolinguistiques et éducatifs sur les représentations élaborées par les personnes interrogées. Ces questionnements permettent de formuler que dans les représentations élaborées par des personnes résidant en Allemagne, en Catalogne et en France, une langue étrangère et une finalité de l’apprentissage de langues étrangères dominent : l’anglais et la fonction utilitariste de la langue.This doctoral thesis seeks to explore and compare representations about forein languages to learn in vocational education in three socio-historical and political entities, Germany, Catalonia and France. It also aims to explore and compare the finalities of learning foreign languages in this kind of education and the eventual influences of political, ideological, sociolinguistical and educational contexts on the representations of the interviewed persons. Those questions allow to formulate that one language and one finality are hegemonical in the representations, english and the utility to learn a foreign language

JERICO. Report after the Strategic workshop # 1 (Heraklion)

One of the main JERICO objectives is to establish a strategy for the future of the coastal observation. In other words, firstly JERICO has both to perform the state of the art with regards to European coastal observation systems and to help harmonizing technologies and sharing knowledge. Then according to the results of this first stage, the project will deliver a strategic plan to step forward. As a starting point, a roadmap was written in deliverable D1.2 “Rationale and Definitions for a Common Strategy” to give a framework to the project participants and inform about intentions. The following step in the process was to organise a strategic workshop #1 which is reported in this document. In the following report presentations made during the workshop are exposed. The first part of the minutes report is dedicated to examples of national coastal observation strategies from: • USA: Janet Newton, University of Washington • France: Patrick Farcy, IFREMER. • Greece: Georges Petihakis, HCMR • Germany: Wilhelm Petersen, COSYNA. • Spain: Julien Mader, AZTI. • Spain: Joaquin Tintore, CSIC-IMEDEA. • Ireland: Glenn Nolan,MI. • UK: David Hydes, NERC. In the second part of the workshop minutes, discussions on the potential future strategy for the coastal observatories in Europe are reviewed, as well as discussions on the possible lobbying to support the future implementation of the future strategy. This last part is a starting point to set in motion a common reflection on a European strategy for coastal observatories. Instead of only reporting the words and discussions occurred during the meeting, authors also report their analysis of the given information in order to put forward specific issues with regards to the national strategies: gathered information with regards to common issues specific to build a strategy for the future: - the scientific strategy, - the infrastructure integration in a national or regional observation system; - the strategy for innovation and to better link with the private sector, - the strategy to flow the data in an integrated data management system and to communicate with scientists, stakeholders and general public. To conclude with this document authors analyses the gathered information versus the missing one in order to better focus the upcoming work and the next workshop. Conclusions also highlight the need of a coordinated implementation and encompassing European governance and the necessity to enhance the links with modeling community

Histological analysis of retrorsin and 2-AAF treated rat liver after genetic labeling of mature hepatocytes in adult animals.

<p><u>Retrorsin model</u>. (A) β-galactosidase positive cells gathered in clusters of small hepatocyte day 15. (B) same clusters at day 30 post hepatectomy. <u>2-AAF model.</u> Immunohistochemical detection of CKs (C), GGT (D), and β-catenin (E) expressed by oval cells. (F) Clusters of β-galactosidase positive hepatocyte observed in the 2-AAF model. All sections are hematoxylin counterstained. All magnifications: ×400 except ×200 B and F.</p

Histological analysis of the retrorsin model after genetic labeling of liver cells in newborn rats.

<p><u>Retrorsin model</u>. (A) Cluster of SHPCs positive for β-galactosidase. (B) Hematoxylin and eosin staining showing large number of merging clusters 30 days post hepatectomy. (C) Immunohistochemical detection of CKs day 30 post hepatectomy. Oval cells are not detected. Hematoxylin counterstain. Magnification: ×200 A–B: ×400 C.</p

Quantification of the number of β-galactosidase positive hepatocytes in the liver of rat labeled at adulthood and treated with Retrorsine (upper panel) or 2-AAF (lower panel).

<p>Quantification of the number of β-galactosidase positive hepatocytes in the liver of rat labeled at adulthood and treated with Retrorsine (upper panel) or 2-AAF (lower panel).</p

Schematic diagrams of retrorsine and 2-AAF treatments.

<p>Schematic diagrams of retrorsine and 2-AAF treatments.</p