Goulphar: rapid access and expertise for standard two-color microarray normalization methods

BACKGROUND: Raw data normalization is a critical step in microarray data analysis because it directly affects data interpretation. Most of the normalization methods currently used are included in the R/BioConductor packages but it is often difficult to identify the most appropriate method. Furthermore, the use of R commands for functions and graphics can introduce mistakes that are difficult to trace. We present here a script written in R that provides a flexible means of access to and monitoring of data normalization for two-color microarrays. This script combines the power of BioConductor and R analysis functions and reduces the amount of R programming required. RESULTS: Goulphar was developed in and runs using the R language and environment. It combines and extends functions found in BioConductor packages (limma and marray) to correct for dye biases and spatial artifacts. Goulphar provides a wide range of optional and customizable filters for excluding incorrect signals during the pre-processing step. It displays informative output plots, enabling the user to monitor the normalization process, and helps adapt the normalization method appropriately to the data. All these analyses and graphical outputs are presented in a single PDF report. CONCLUSION: Goulphar provides simple, rapid access to the power of the R/BioConductor statistical analysis packages, with precise control and visualization of the results obtained. Complete documentation, examples and online forms for setting script parameters are available from

Littéracies universitaires : accompagnement et autonomisation dans l’apprentissage des écrits de et à l’université

Ce numéro thématique est issu du croisement de deux projets. Le premier projet était consacré aux littéracies universitaires dans une collaboration scientifique d’envergure entre des chercheurs de trois universités françaises et quatre brésiliennes (Capes-COFECUB SH 834-15 2015-2018; Bailly et al., 2016a). Le second projet touche à la pédagogie universitaire et plus précisément à la préoccupation enseignante de mettre en place des dispositifs pour que tous les étudiants réussissent leurs appr..

Apprendre à écrire en anglais scientifique dans le secteur Lansad en master : quelles aides pour l’autonomisation des étudiants?

Etant donnée la diversité croissante des publics de l’université et leurs hétérogénéités linguistiques et langagières, le cours d’anglais scientifique du master didactique des langues/fle de l’Université de Lorraine (UL) se présente depuis 2014 sous la forme d’un dispositif d’apprentissage autodirigé avec soutien. Les étudiants peuvent aller à leur rythme et bénéficier d’un accompagnement personnalisé. Pour valider ce cours, les étudiants doivent rédiger un texte scientifique long en anglais dans leur discipline, de manière autorégulée et à l’aide d’une variété de ressources mises à leur disposition en appui sur la plateforme de cours de l’UL. Ces ressources sont censées d’une part aider la construction autonome de connaissances et de compétences qui s’articulent dans l’acte d’écriture scientifique en anglais, et d’autre part, soutenir le processus d’auto-régulation et d’autonomisation dans ses dimensions cognitives et affectives. Pour cette recherche, nous analysons le design du système d’aide proposé, ainsi que ses effets à partir de questionnaires d’évaluation du cours proposés en fin de semestre. Les résultats indiquent que les étudiants ont trouvé ce cours difficile mais que les aides à l’implication et l’accrochage à la tâche demandée, ingrédients importants de l’autorégulation, ont été efficientes. Parmi les modalités d’aide proposées, les préférées sont celles qui impliquent une interaction directe entre l’enseignante et les étudiants à l’oral et à l’écrit, comme l’entretien de conseil et le journal de bord.To cope with the growing diversity and linguistic heterogeneity of the student population at the University of Lorraine (UL), a self-directed English for (written) Academic Purposes course was designed in 2014 for the Master’s students of Didactique des langues/fle. Students can make progress at their own pace and benefit from personalised support. To complete this course, the students must write a long scientific text in English, making use of self-regulated practices and a variety of resources made available to them on the UL course platform. These resources support, on the one hand, the building of new knowledge and skills needed to successfully complete the required task, and on the other hand, learner autonomy and self-regulation steeped in cognitive and affective dimensions. For the purposes of this study, we will analyse the design of the support system offered as well as its effects, by making use of assessment questionnaires provided at the end of the semester. Results indicate that although the students found the course difficult, the efficiency of the aid to support their engagement and adherence to the required task, which are important ingredients of self-regulation. Among the different kinds of aids offered, students prefer those that involve direct oral or written interaction with the teacher, such as one-to-one advisory sessions and the logbook

Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells

BACKGROUND: Endometrial cancer is the fourth most prominent cancer among all feminine cancers in the Western world. Resveratrol, a natural anti-oxidant found in red wine emerging as a novel anticancer agent, exerts antiproliferative and pro-apoptotic activity in various cancer cell types, but its effect on uterine cancer cells is poorly understood. At the molecular level, resveratrol has been reported to inhibit cyclooxygenase (COX) expression and/or activity; in endometrial cancer cells, COX-2 is overexpressed and confers cellular resistance to apoptosis. The aim of the present study was to determine if resveratrol could exert anti-proliferative and pro-apoptotic activity over uterine cancer cells upon inhibition of COX-2 expression and/or activity. Six different human uterine cancer cell lines were used as a model (HeLa, Hec-1A, KLE, RL95-2, Ishikawa and EN-1078D). RESULTS AND DISCUSSION: High-dose of resveratrol triggered apoptosis in five out of six uterine cancer cell lines, as judged from Hoechst nuclear staining and effector caspase cleavage. In accordance, uterine cancer cell proliferation was decreased. Resveratrol also reduced cellular levels of the phosphorylated/active form of anti-apoptotic kinase AKT. Endogenous COX-2 protein levels were decreased, concomitant with a decrease in production of COX metabolites PGE2 and PGF2α, in each uterine cancer cell line expressing detectable levels of COX-1 and/or COX-2 in presence of resveratrol. Although COX expression was identified as a target of resveratrol in uterine cancer cells, inhibition of COX activity or exogenously added PGE2 did not modulate the effect of resveratrol on cellular proliferation. CONCLUSION: High-dose of resveratrol exerts tumoricidal activity over uterine cancer cells and regulates COX expression. In these cells, resveratrol would not directly target COX activity, but possibly other enzymes involved in prostaglandin synthesis that act downstream of the COXs

Structure and properties of transcriptional networks driving selenite stress response in yeasts

<p>Abstract</p> <p>Background</p> <p>Stress responses provide valuable models for deciphering the transcriptional networks controlling the adaptation of the cell to its environment. We analyzed the transcriptome response of yeast to toxic concentrations of selenite. We used gene network mapping tools to identify functional pathways and transcription factors involved in this response. We then used chromatin immunoprecipitation and knock-out experiments to investigate the role of some of these regulators and the regulatory connections between them.</p> <p>Results</p> <p>Selenite rapidly activates a battery of transcriptional circuits, including iron deprivation, oxidative stress and protein degradation responses. The mRNA levels of several transcriptional regulators are themselves regulated. We demonstrate the existence of a positive transcriptional loop connecting the regulator of proteasome expression, Rpn4p, to the pleiotropic drug response factor, Pdr1p. We also provide evidence for the involvement of this regulatory module in the oxidative stress response controlled by the Yap1p transcription factor and its conservation in the pathogenic yeast <it>C. glabrata</it>. In addition, we show that the drug resistance regulator gene <it>YRR1 </it>and the iron homeostasis regulator gene <it>AFT2 </it>are both directly regulated by Yap1p.</p> <p>Conclusion</p> <p>This work depicted a highly interconnected and complex transcriptional network involved in the adaptation of yeast genome expression to the presence of selenite in its chemical environment. It revealed the transcriptional regulation of <it>PDR1 </it>by Rpn4p, proposed a new role for the pleiotropic drug resistance network in stress response and demonstrated a direct regulatory connection between oxidative stress response and iron homeostasis.</p

Intense exercise training induces adaptation in expression and responsiveness of cardiac β-adrenoceptors in diabetic rats

<p>Abstract</p> <p>Background</p> <p>Informations about the effects of intense exercise training on diabetes-induced myocardial dysfunctions are lacking. We have examined the effects of intense exercise training on the cardiac function of diabetic rats, especially focusing on the Langendorff β-adrenergic responsiveness and on the β-adrenoceptors protein expression.</p> <p>Methods</p> <p>Control or Streptozotocin induced-diabetic male Wistar rats were randomly assigned to sedentary or trained groups. The training program consisted of 8 weeks running on a treadmill (10° incline, up to 25 m/min, 60 min/day) and was considered to be intense for diabetic rats.</p> <p>Results</p> <p>This intense exercise training amplified the <it>in vivo </it>diabetes-induced bradycardia. It had no effect on Langendorff basal cardiac contraction and relaxation performances in control and diabetic rats. In diabetic rats, it accentuated the Langendorff reduced responsiveness to β-adrenergic stimulation. It did not blunt the diabetes-induced decrease of β1-adrenoceptors protein expression, displayed a significant decrease in the β2-adrenoceptors protein expression and normalized the β3-adrenoceptors protein expression.</p> <p>Conclusions</p> <p>Intense exercise training accentuated the decrease in the myocardial responsiveness to β-adrenergic stimulation induced by diabetes. This defect stems principally from the β2-adrenoceptors protein expression reduction. Thus, these results demonstrate that intense exercise training induces specific effects on the β-adrenergic system in diabetes.</p

Ploidy influences cellular responses to gross chromosomal rearrangements in saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Gross chromosomal rearrangements (GCRs) such as aneuploidy are key factors in genome evolution as well as being common features of human cancer. Their role in tumour initiation and progression has not yet been completely elucidated and the effects of additional chromosomes in cancer cells are still unknown. Most previous studies in which <it>Saccharomyces cerevisiae </it>has been used as a model for cancer cells have been carried out in the haploid context. To obtain new insights on the role of ploidy, the cellular effects of GCRs were compared between the haploid and diploid contexts.</p> <p>Results</p> <p>A total number of 21 haploid and diploid <it>S. cerevisiae </it>strains carrying various types of GCRs (aneuploidies, nonreciprocal translocations, segmental duplications and deletions) were studied with a view to determining the effects of ploidy on the cellular responses. Differences in colony and cell morphology as well as in the growth rates were observed between mutant and parental strains. These results suggest that cells are impaired physiologically in both contexts. We also investigated the variation in genomic expression in all the mutants. We observed that gene expression was significantly altered. The data obtained here clearly show that genes involved in energy metabolism, especially in the tricarboxylic acid cycle, are up-regulated in all these mutants. However, the genes involved in the composition of the ribosome or in RNA processing are down-regulated in diploids but up-regulated in haploids. Over-expression of genes involved in the regulation of the proteasome was found to occur only in haploid mutants.</p> <p>Conclusion</p> <p>The present comparisons between the cellular responses of strains carrying GCRs in different ploidy contexts bring to light two main findings. First, GCRs induce a general stress response in all studied mutants, regardless of their ploidy. Secondly, the ploidy context plays a crucial role in maintaining the stoichiometric balance of the proteins: the translation rates decrease in diploid strains, whereas the excess protein synthesized is degraded in haploids by proteasome activity.</p

Rapid assembly of the polyhydroxylated b-amino acid constituents of microsclerodermins C, D et E.

A very short and efficient synthesis of protected derivatives of APTO and AETD, the complex polyhydroxylated -amino acid residues present in microsclerodermins C, D, and E, is described. The targets are obtained in only five steps, in 23% and 16% overall yields, respectively. The key transformation involves the completely diastereoselective two-carbon homologation of appropriately selected intermediate chiral sulfinimine

Identification of novel genes potentially involved in somatic embryogenesis in chicory (Cichorium intybus L.)

<p>Abstract</p> <p>Background</p> <p>In our laboratory we use cultured chicory (<it>Cichorium intybus</it>) explants as a model to investigate cell reactivation and somatic embryogenesis and have produced 2 chicory genotypes (K59, C15) sharing a similar genetic background. K59 is a responsive genotype (embryogenic) capable of undergoing complete cell reactivation <it>i.e</it>. cell de- and re-differentiation leading to somatic embryogenesis (SE), whereas C15 is a non-responsive genotype (non-embryogenic) and is unable to undergo SE. Previous studies <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> showed that the use of the β-D-glucosyl Yariv reagent (β-GlcY) that specifically binds arabinogalactan-proteins (AGPs) blocked somatic embryo production in chicory root explants. This observation indicates that β-GlcY is a useful tool for investigating somatic embryogenesis (SE) in chicory. In addition, a putative AGP (DT212818) encoding gene was previously found to be significantly up-regulated in the embryogenic K59 chicory genotype as compared to the non-embryogenic C15 genotype suggesting that this AGP could be involved in chicory re-differentiation <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. In order to improve our understanding of the molecular and cellular regulation underlying SE in chicory, we undertook a detailed cytological study of cell reactivation events in K59 and C15 genotypes, and used microarray profiling to compare gene expression in these 2 genotypes. In addition we also used β-GlcY to block SE in order to identify genes potentially involved in this process.</p> <p>Results</p> <p>Microscopy confirmed that only the K59, but not the C15 genotype underwent complete cell reactivation leading to SE formation. β-GlcY-treatment of explants blocked <it>in vitro </it>SE induction, but not cell reactivation, and induced cell wall modifications. Microarray analyses revealed that 78 genes were differentially expressed between induced K59 and C15 genotypes. The expression profiles of 19 genes were modified by β-GlcY-treatment. Eight genes were both differentially expressed between K59 and C15 genotypes during SE induction and transcriptionally affected by β-GlcY-treatment: <it>AGP </it>(DT212818), <it>26 S proteasome AAA ATPase subunit 6 </it>(<it>RPT6</it>), <it>remorin </it>(<it>REM</it>), <it>metallothionein-1 </it>(<it>MT1</it>), two non-specific lipid transfer proteins genes (<it>SDI-9 and DEA1</it>), <it>3-hydroxy-3-methylglutaryl-CoA reductase </it>(<it>HMG-CoA reductase</it>), and <it>snakin 2 </it>(<it>SN2</it>). These results suggest that the 8 genes, including the previously-identified <it>AGP </it>gene (DT212818), could be involved in cell fate determination events leading to SE commitment in chicory.</p> <p>Conclusion</p> <p>The use of two different chicory genotypes differing in their responsiveness to SE induction, together with β-GlcY-treatment represented an efficient tool to discriminate cell reactivation from the SE morphogenetic pathway. Such an approach, together with microarray analyses, permitted us to identify several putative key genes related to the SE morphogenetic pathway in chicory.</p

Relevance of MRI for management of non-displaced lateral humeral condyle fractures in children

INTRODUCTION: The treatment for non-displaced (<2 mm displacement) fractures of the lateral humeral condyle in children is controversial. Most studies recommend non-surgical treatment. However, plain radiographs are not sufficient to evaluate extension of the fracture line through the articular cartilage. This explains the high frequency of secondary displacements and non-unions, despite well-conducted conservative treatment. We hypothesized that MRI could be used to analyse whether the fracture is complete or incomplete. This could help to determine whether surgical or conservative treatment is indicated. MATERIAL AND METHODS: This prospective study enrolled children being treated for a non-displaced (< 2 mm gap) fracture of the lateral humeral condyle. All patients were treated with a long-arm cast in the emergency room. An MRI was done later on without sedation. A specific protocol was used to reduce the duration of the examination. T2-weighted and proton density fat-saturated sequences were used. RESULTS: Twenty-seven patients were enrolled: 16 boys and 11 girls with a mean age of 5 years (2-10). The MRI was performed an average of 7 days (1-23) after the fracture. The MRI could not be interpreted in two cases because the child had moved during the examination. In the other 25 patients, the fracture was incomplete in 17 patients and complete in 8 patients. Two children had secondary displacement diagnosed 7 and 11 days after the fracture event. These two patients underwent open reduction and internal fixation. There was no correlation between patient age and the fracture being complete or incomplete. There were no cases of non-union. CONCLUSION: MRI appears to be a reliable method for determining whether the fracture line is complete or incomplete. It can be performed without sedation, even in children as young as 2 years of age. Use of an injury-specific MRI protocol reduces the length of the examination, thereby improving its performance. We recommend that it be used to analyse non-displaced fractures of the lateral humeral condyle in children