Androgen-induced masculinization in rainbow trout results in a marked dysregulation of early gonadal gene expression profiles

<p>Abstract</p> <p>Background</p> <p>Fish gonadal sex differentiation is affected by sex steroids treatments providing an efficient strategy to control the sexual phenotype of fish for aquaculture purposes. However, the biological effects of such treatments are poorly understood. The aim of this study was to identify the main effects of an androgen masculinizing treatment (11β-hydroxyandrostenedione, 11βOHΔ4, 10 mg/kg of food for 3 months) on gonadal gene expression profiles of an all-female genetic population of trout. To characterize the most important molecular features of this process, we used a large scale gene expression profiling approach using rainbow trout DNA microarrays combined with a detailed gene ontology (GO) analysis.</p> <p>Results</p> <p>2,474 genes were characterized as up-regulated or down-regulated in trout female gonads masculinized by androgen in comparison with control male or female gonads from untreated all-male and all-female genetic populations. These genes were classified in 13 k-means clusters of temporally correlated expression profiles. Gene ontology (GO) data mining revealed that androgen treatment triggers a marked down-regulation of genes potentially involved in early oogenesis processes (GO 'mitotic cell cycle', 'nucleolus'), an up-regulation of the translation machinery (GO 'ribosome') along with a down-regulation of proteolysis (GO 'proteolysis', 'peptidase' and 'metallopeptidase activity'). Genes considered as muscle fibres markers (GO 'muscle contraction') and genes annotated as structural constituents of the extracellular matrix (GO 'extracellular matrix') or related to meiosis (GO 'chromosome' and 'meiosis') were found significantly enriched in the two clusters of genes specifically up-regulated in androgen-treated female gonads. GO annotations 'Sex differentiation' and 'steroid biosynthesis' were enriched in a cluster of genes with high expression levels only in control males. Interestingly none of these genes were stimulated by the masculinizing androgen treatment.</p> <p>Conclusion</p> <p>This study provides evidence that androgen masculinization results in a marked dysregulation of early gene expression profiles when compared to natural testicular or ovarian differentiation. Based on these results we suggest that, in our experimental conditions, androgen masculinization proceeds mainly through an early inhibition of female development.</p

Expression profiling of prospero in the Drosophila larval chemosensory organ: Between growth and outgrowth

<p>Abstract</p> <p>Background</p> <p>The antenno-maxilary complex (AMC) forms the chemosensory system of the <it>Drosophila </it>larva and is involved in gustatory and olfactory perception. We have previously shown that a mutant allele of the homeodomain transcription factor Prospero (<it>prosVoila1</it>, <it>V1</it>), presents several developmental defects including abnormal growth and altered taste responses. In addition, many neural tracts connecting the AMC to the central nervous system (CNS) were affected. Our earlier reports on larval AMC did not argue in favour of a role of <it>pros </it>in cell fate decision, but strongly suggested that <it>pros </it>could be involved in the control of other aspect of neuronal development. In order to identify these functions, we used microarray analysis of larval AMC and CNS tissue isolated from the wild type, and three other previously characterised <it>prospero </it>alleles, including the <it>V1 </it>mutant, considered as a null allele for the AMC.</p> <p>Results</p> <p>A total of 17 samples were first analysed with hierarchical clustering. To determine those genes affected by loss of <it>pros </it>function, we calculated a discriminating score reflecting the differential expression between <it>V1 </it>mutant and other <it>pros </it>alleles. We identified a total of 64 genes in the AMC. Additional manual annotation using all the computed information on the attributed role of these genes in the <it>Drosophila </it>larvae nervous system, enabled us to identify one functional category of potential Prospero target genes known to be involved in neurite outgrowth, synaptic transmission and more specifically in neuronal connectivity remodelling. The second category of genes found to be differentially expressed between the null mutant AMC and the other alleles concerned the development of the sensory organs and more particularly the larval olfactory system. Surprisingly, a third category emerged from our analyses and suggests an association of <it>pros </it>with the genes that regulate autophagy, growth and insulin pathways. Interestingly, EGFR and Notch pathways were represented in all of these three functional categories. We now propose that Pros could perform all of these different functions through the modulation of these two antagonistic and synergic pathways.</p> <p>Conclusions</p> <p>The current data contribute to the clarification of the <it>prospero </it>function in the larval AMC and show that <it>pros </it>regulates different function in larvae as compared to those controlled by this gene in embryos. In the future, the possible mechanism by which Pros could achieve its function in the AMC will be explored in detail.</p

Lecture publique et intercommunalité : quatre exemples normands

Mémoire d\u27étude de Master portant sur la lecture publique et l\u27intercommunalité en Normandie

Le lymphome primitif de la prostate : à propos d’un cas avec revue de la literature

Le lymphome primitif de la prostate est une affection maligne rare. Les patients présentent initialement des signes urinaires locaux et des signes généraux. Plusieurs traitements ont été utilisés comme la prostatectomie radicale, la radiothérapie ou des associations de chimiothérapie et de radiothérapie. Une revue de la littérature fait état du mauvais pronostic du lymphome de la prostate, le diagnostic se faisant souvent à un stade tardif. Nous rapportons le cas d’un patient âgé de 73 ans présentant une rétention aiguë d’urines dans un contexte de constipation opiniâtre avec amaigrissement sévère. Il était diabétique, aux antécédents de carcinome urothélial de stade pT1 et de grade G3, traité par résection transurétrale et BCG thérapie. L’examen clinique a révélé une prostate très augmentée de volume, ce qui a été confirmé par les examens d’imagerie. L’analyseanatomo-pathologique des biopsies réalisées par voie transrectale a mis en évidence un lymphome malin non Hodgkinien de type B primitif de la prostate. La prise en charge a consisté en une chimiothérapie. Malgré une régression considérable du volume tumoral à partir de la troisièmesemaine, le patient est décédé au lendemain de son 5ème cycle de chimiothérapie

Regulation of intestinal epithelial cells transcriptome by enteric glial cells: impact on intestinal epithelial barrier functions

<p>Abstract</p> <p>Background</p> <p>Emerging evidences suggest that enteric glial cells (EGC), a major constituent of the enteric nervous system (ENS), are key regulators of intestinal epithelial barrier (IEB) functions. Indeed EGC inhibit intestinal epithelial cells (IEC) proliferation and increase IEB paracellular permeability. However, the role of EGC on other important barrier functions and the signalling pathways involved in their effects are currently unknown. To achieve this goal, we aimed at identifying the impact of EGC upon IEC transcriptome by performing microarray studies.</p> <p>Results</p> <p>EGC induced significant changes in gene expression profiling of proliferating IEC after 24 hours of co-culture. 116 genes were identified as differentially expressed (70 up-regulated and 46 down-regulated) in IEC cultured with EGC compared to IEC cultured alone. By performing functional analysis of the 116 identified genes using Ingenuity Pathway Analysis, we showed that EGC induced a significant regulation of genes favoring both cell-to-cell and cell-to-matrix adhesion as well as cell differentiation. Consistently, functional studies showed that EGC induced a significant increase in cell adhesion. EGC also regulated genes involved in cell motility towards an enhancement of cell motility. In addition, EGC profoundly modulated expression of genes involved in cell proliferation and cell survival, although no clear functional trend could be identified. Finally, important genes involved in lipid and protein metabolism of epithelial cells were shown to be differentially regulated by EGC.</p> <p>Conclusion</p> <p>This study reinforces the emerging concept that EGC have major protective effects upon the IEB. EGC have a profound impact upon IEC transcriptome and induce a shift in IEC phenotype towards increased cell adhesion and cell differentiation. This concept needs to be further validated under both physiological and pathophysiological conditions.</p

Feature extraction and signal processing for nylon DNA microarrays

BACKGROUND: High-density DNA microarrays require automatic feature extraction methodologies and softwares. These can be a potential source of non-reproducibility of gene expression measurements. Variation in feature location or in signal integration methodology may be a significant contribution to the observed variance in gene expression levels. RESULTS: We explore sources of variability in feature extraction from DNA microarrays on Nylon membrane with radioactive detection. We introduce a mathematical model of the signal emission and derive methods for correcting biases such as overshining, saturation or variation in probe amount. We also provide a quality metric which can be used qualitatively to flag weak or untrusted signals or quantitatively to modulate the weight of each experiment or gene in higher level analyses (clustering or discriminant analysis). CONCLUSIONS: Our novel feature extraction methodology, based on a mathematical model of the radioactive emission, reduces variability due to saturation, neighbourhood effects and variable probe amount. Furthermore, we provide a fully automatic feature extraction software, BZScan, which implements the algorithms described in this paper

MADGene: retrieval and processing of gene identifier lists for the analysis of heterogeneous microarray datasets

Summary: MADGene is a software environment comprising a web-based database and a java application. This platform aims at unifying gene identifiers (ids) and performing gene set analysis. MADGene allows the user to perform inter-conversion of clone and gene ids over a large range of nomenclatures relative to 17 species. We propose a set of 23 functions to facilitate the analysis of gene sets and we give two microarray applications to show how MADGene can be used to conduct meta-analyses