Review: Pancreatic β-Cell Neogenesis Revisited

β-cell neogenesis triggers the generation of new β-cells from precursor cells. Neogenesis from duct epithelium is the most currently described and the best documented process of differentiation of precursor cells into β-cells. It is contributes not only to β-cell mass expansion during fetal and nonatal life but it is also involved in the maintenance of the β-cell mass in adults. It is also required for the increase in β-cell mass in situations of increase insulin demand (obesity, pregnancy). A large number of factors controlling the differentiation of β-cells has been identified. They are classified into the following main categories: growth factors, cytokine and inflamatory factors, and hormones such as PTHrP and GLP-1. The fact that intestinal incretin hormone GLP-1 exerts a major trophic role on pancreatic β-cells provides insights into the possibility to pharmacologically stimulate β-cell neogenesis. This could have important implications for the of treatment of type 1 and type 2 diabetes. Transdifferentiation, that is, the differentiation of already differentiated cells into β-cells, remains controversial.However, more and more studies support this concept. The cells, which can potentially “transdifferentiate” into β-cells, can belong to the pancreas (acinar cells) and even islets, or originate from extra-pancreatic tissues such as the liver. Neogenesis from intra-islet precursors also have been proposed and subpopulations of cell precursors inside islets have been described by some authors. Nestin positive cells, which have been considered as the main candidates, appear rather as progenitors of endothelial cells rather than β-cells and contribute to angiogenesis rather than neogenesis. To take advantage of the different differentiation processes may be a direction for future cellular therapies. Ultimately, a better understanding of the molecular mechanisms involved in β-cell neogenesis will allow us to use any type of differentiated and/or undifferentiated cells as a source of potential cell precursors

In quest of legitimacy: The theoretical and methodological foundations of entrepreneurship education research

This editorial discusses contemporary entrepreneurship education research and identifies the manner in which the three articles comprising this special issue contribute to advancing the theoretical and methodological foundations of the field. In so doing we seek to describe how and why entrepreneurship education research may struggle for legitimacy along with the complexities of working in this field. This special issue raises questions about entrepreneurship education research and, through the featured articles provides some responses. This special issue itself, however, is presented as part of an ongoing discussion about the nature and role of entrepreneurship education more widely and is intended to provoke further critical engagement and stimulate theoretical and methodological development

La Bibliothèque HOA, Bilan et Perspectives

International audienceCet article présente l’état actuel de la bibliothèque HOA en cours de développement, suite à un premier article paru dans les actes des Jim 2012. Nousprésentons en détail l’ensemble des objets. Nous précisons l’apport de la décomposition en ondes planes dans le contexte ambisonique ainsi que l’usage de la synthèse binaurale pour une ambisonie virtuelle. Enfin nous abordons la prise en main de la bibliothèque par les musiciens

On combining wavelets expansion and sparse linear models for Regression on metabolomic data and biomarker selection

International audienceWavelet thresholding of spectra has to be handled with care when the spectra are the predictors of a regression problem. Indeed, a blind thresholding of the signal followed by a regression method often leads to deteriorated predictions. The scope of this article is to show that sparse regression methods, applied in the wavelet domain, perform an automatic thresholding: the most relevant wavelet coefficients are selected to optimize the prediction of a given target of interest. This approach can be seen as a joint thresholding designed for a predictive purpose. The method is illustrated on a real world problem where metabolomic data are linked to poison ingestion. This example proves the usefulness of wavelet expansion and the good behavior of sparse and regularized methods. A comparison study is performed between the two-steps approach (wavelet thresholding and regression) and the one-step approach (selection of wavelet coefficients with a sparse regression). The comparison includes two types of wavelet bases, various thresholding methods, and various regression methods and is evaluated by calculating prediction performances. Information about the location of the most important features on the spectra was also obtained and used to identify the most relevant metabolites involved in the mice poisoning

Specificity of the metabolic signatures of fish from cyanobacteria rich lakes

International audienceThe liver metabolomes of fish from cyanobacterial-dominated ponds were investigated. Cyanobacterial metabolites were only be detected in cyanobacterial dominated ponds. The metabolomes of the 2 fish species exhibit similar correlation with cyanobacteria occurrence. Correlations between the levels of some metabolites and phycocyanin or pH were observed. a b s t r a c t With the increasing impact of the global warming, occurrences of cyanobacterial blooms in aquatic ecosystems are becoming a main worldwide ecological concern. Due to their capacity to produce potential toxic metabolites, interactions between the cyanobacteria, their cyanotoxins and the surrounding freshwater organisms have been investigated during the last past years. Non-targeted metabolomic analyses have the powerful capacity to study simultaneously a high number of metabolites and thus to investigate in depth the molecular signatures between various organisms encountering different environmental scenario, and potentially facing cyanobacterial blooms. In this way, the liver metabolomes of two fish species (Perca fluviatilis and Lepomis gibbosus) colonizing various peri-urban lakes of theÎle-de-France region displaying high biomass of cyanobacteria, or not, were investigated. The fish metabolome hydrophilic fraction was analyzed by 1 H NMR analysis coupled with Batman peak treatment for the quantification and the annotation attempt of the metabolites. The results suggest that similar metabolome profiles occur in both fish species, for individuals collected from cyanobacterial blooming lakes compared to organism from non-cyanobacterial dominant environments. Overall, such environmental metabolomic pilot study provides new research perspectives in ecology and ecotoxicology fields, and may notably provide new information concerning the cyanobacteria/fish eco-toxicological interactions

Cell proliferation and migration during early development of a symbiotic scleractinian coral

In scleractinian reef-building corals, patterns of cell self-renewal, migration and death remain virtually unknown, limiting our understanding of cellular mechanisms underlying initiation of calcification, and ontogenesis of the endosymbiotic dinoflagellate relationship. In this study, we pulse-labelled the coral Stylophora pistillata for 24 h with BrdU at four life stages (planula, early metamorphosis, primary polyp and adult colony) to investigate coral and endosymbiont cell proliferation during development, while simultaneously recording TUNEL-positive (i.e. apoptotic) nuclei. In the primary polyp, the fate of BrdU-labelled cells was tracked during a 3-day chase. The pharynx and gastrodermis were identified as the most proliferative tissues in the developing polyp, and BrdU-labelled cells accumulated in the surface pseudostratified epithelium and the skeletogenic calicodermis during the chase, revealing cell migration to these epithelia. Surprisingly, the lowest cell turnover was recorded in the calicodermis at all stages, despite active, ongoing skeletal deposition. In dinoflagellate symbionts, DNA synthesis was systematically higher than coral host gastrodermis, especially in planula and early metamorphosis. The symbiont to host cell ratio remained constant, however, indicating successive post-mitotic control mechanisms by the host of its dinoflagellate density in early life stages, increasingly shifting to apoptosis in the growing primary polyp

Phenotypic prediction based on metabolomic data : lasso vs Bolasso, primary data vs wavelet transformation

International audienceUnderstanding the relations between various 'omics data (such as metabolomics or genomics data) and phenotypes of interest is one of the current major challenges in biology. This question can be addressed by trying to learn a way to predict the phenotype value from the omic from joint observations of the omic and of the phenotype. In this paper, we focus on the prediction of a phenotype related to the quality of the meat from metabolomic data. As metabolomic data are high dimensional data and as, conjointly, the number of observations is often restricted, model selection methods are a way both to obtain a relevant solution to the prediction problem but also to select the most important metabolomes related to the phenotype under study. During the past years, model selection has know a growing interest in the statistical community: the first - and also probably the most known - selection method has been introducted by \citep{Tibshirani:1996} under the name of LASSO. Several variants of this original approach has then been proposed such as, recently, a bootstraped LASSO, named BOLASSO, introduced in (Bach, 2009). The proposal of this paper is to combine a wavelet representation of the metabolome spectra (see (Mallat, 1999) and (Antonini, 1992) for a complete introduction to wavelets) with the BOLASSO approach. We compare this methodology to more classical methods using either the original spectra as predictors (instead of the wavelet representation) or the original LASSO to select the model. The following section deals with the methodological description of the approach whereas the next one details the experiments and results

Role of Glucose in IRS Signaling in Rat Pancreatic Islets: Specific Effects and Interplay with Insulin

We investigated the possible interplay between insulin and glucose signaling pathways in rat pancreatic β-cell with a special focus on the role of glucose in IRS signaling in vivo. Three groups of rats were constituted by combining simultaneous infusion during 48 h either of glucose and/or insulin, or glucose+diazoxide: Hyperglycemic- Hyperinsulinemic (HGHI), euglycemic-Hyperinsulinemic (eGHI), Hyperglycemic-euinsulinemic (HGeI). Control rats were infused with 0,9% NaCl. In HGHI and HGeI rats plasma glucose levels were maintained at 20-22 mmol/l. In eGHI rats, plasma glucose was not different from that of controls, whereas plasma insulin was much higher than in controls. In HGHI rats, IRS-2 mRNA expression, total protein and phosphorylated protein amounts were increased compared to controls. In HGeI rats, only IRS-2 mRNA expression was increased. No change was observed in eGHI rats whatever the parameter considered. In all groups, mRNA concentration of IRS-1 was similar to that of controls. The quantity of total and phosphorylated IRS- 1 protein was dramatically increased in HGHI rats and to a lesser extent in eGHI rats. Neither mRNA nor IRS-1 protein expression were modified in HGeI rats. The data suggest that glucose and insulin play at once a specific and a complementary role in islet IRSs signaling. Especially, glucose stimulates IRS-2 mRNA expression whatever the insulin status and independently of the secretory process. The differential regulation of IRS-1 and IRS-2 expressions is in agreement with their supposed different involvement in the control of β-cell growth and function