Orchestrated transcription of biological processes in the marine picoeukaryote Ostreococcus exposed to light/dark cycles

Background: Picoeukaryotes represent an important, yet poorly characterized component of marine phytoplankton. The recent genome availability for two species of Ostreococcus and Micromonas has led to the emergence of picophytoplankton comparative genomics. Sequencing has revealed many unexpected features about genome structure and led to several hypotheses on Ostreococcus biology and physiology. Despite the accumulation of genomic data, little is known about gene expression in eukaryotic picophytoplankton. Results: We have conducted a genome-wide analysis of gene expression in Ostreococcus tauri cells exposed to light/dark cycles (L/D). A Bayesian Fourier Clustering method was implemented to cluster rhythmic genes according to their expression waveform. In a single L/D condition nearly all expressed genes displayed rhythmic patterns of expression. Clusters of genes were associated with the main biological processes such as transcription in the nucleus and the organelles, photosynthesis, DNA replication and mitosis. Conclusions: Light/Dark time-dependent transcription of the genes involved in the main steps leading to protein synthesis (transcription basic machinery, ribosome biogenesis, translation and aminoacid synthesis) was observed, to an unprecedented extent in eukaryotes, suggesting a major input of transcriptional regulations in Ostreococcus. We propose that the diurnal co-regulation of genes involved in photoprotection, defence against oxidative stress and DNA repair might be an efficient mechanism, which protects cells against photo-damage thereby, contributing to the ability of O. tauri to grow under a wide range of light intensities

L'innovation technologique et la co-production des services comptables dans les fiduciaires

peer reviewedIncreasingly, emerging information technologies such as shared software and continuous accounting are offering alternative ways to perform accounting tasks in a supposedly more efficient fashion. Yet, few studies have investigated how they affect the provision of accounting services, especially in the context of small accounting firms, which provide legal and tax services to entrepreneurs and businesses. Drawing on the service perspective, the paper critically examines how technological innovation challenges and reconfigures the co-production of accounting services in these firms

Mise au point du dosage d’ajmaline, de yohimbine et de réserpine par CL-HR-SM : application à un cas d’intoxication mortelle

National audienceObjectif L’ibogaïne, alcaloïde extrait de Tabernanthe iboga, est depuis longtemps utilisé en Afrique de l’Ouest à des fins rituelles ou de médication. Depuis quelques années, cette substance est proposée pour lutter contre les addictions, en particulier à l’alcool et aux opiacés [1]. Nous présentons les données médico-légales, cliniques et analytiques concernant une femme de 30 ans dépendante à l’héroïne, retrouvée décédée, et pouvant avoir consommé une poudre achetée via Internet étiquetée « Iboga du Gabon ». Nous présentons également les données relatives à l’identification et à l’analyse de cette poudre, e les corrélations avec les conclusions de l’autopsie. Méthodes La poudre et les prélèvements biologiques (sang périphérique et bile) ont été extraits et analysés selon une méthode de screening par un couplage LC-MS en haute résolution (Q Exactive®, Thermo Scientific) sur une colonne Gold PFP (150 × 2,1 mm, 5 μm). Une méthode de dosage a été développée pour quantifier dans le sang et la bile les alcaloïdes identifiés dans la poudre : après ajout de l’EI (flurazépam), 100 μL d’échantillon sont extraits en phase liquide en milieu basique, évaporés à sec et repris par 500 μL de phase mobile puis analysés par CL-HR-SM en mode MS/MS. L’ajmaline, la yohimbine, le flurazepam et la réserpine présentent respectivement des temps de rétention de 3,0 ; 3,2 ; 3,8 et 4,6 min et des transitions de détection 327,2060 → 144,0805 ; 355,2050 → 144,0805 ; 388,1586 → 315,0686 ; 609,2796 → 174,0911. Les concentrations sanguines ont été déterminées au moyen de courbes de calibration (corrélation > 0,99) allant de 10 à 1000 ng/mL obtenues en surchargeant du sang par les alcaloïdes. Résultats Le screening réalisé dans la poudre et les prélèvements biologiques ont permis de mettre en évidence la présence d’ajmaline, yohimbine et réserpine (Tableau 1). Les analyses ont également révélé la présence dans le sang d’oxazépam, de norbuprénorphine et du glucuronide de morphine à des concentrations thérapeutiques usuelles. Conclusion La poudre étiquetée iboga n’en contient pas. Les alcaloïdes qu’elle contient, également retrouvés dans le sang, laissent suggérer une falsification par une autre espèce végétale proche : Rauwolfia sp. Cette confusion est décrite depuis de nombreuses années sous l’appellation « faux iboga ». La toxicité des alcaloïdes est différente, avec notamment des risques cardiovasculaires qui justifient des mesures d’information et de prévention pour les usagers éventuels de ces pratiques. L’imputabilité du décès à la consommation de la poudre peut donc être envisagée

The expression of EMX2 lead to cell cycle arrest in glioblastoma cell line

Abstract Background Glioblastoma (GB) is a highly invasive primary brain tumor that nearly always systematically recurs at the site of resection despite aggressive radio-chemotherapy. Previously, we reported a gene expression signature related to tumor infiltration. Within this signature, the EMX2 gene encodes a homeodomain transcription factor that we found was down regulated in glioblastoma. As EMX2 is reported to play a role in carcinogenesis, we investigated the impact of EMX2 overexpression in glioma-related cell lines. Methods For that purpose, we constructed tetracycline-inducible EMX2 expression lines. Transfected cell phenotypes (proliferation, cell death and cell cycle) were assessed in time-course experiments. Results Restoration of EMX2 expression in U87 glioblastoma cells significantly inhibited cell proliferation. This inhibition was reversible after EMX2 removal from cells. EMX2-induced proliferative inhibition was very likely due to cell cycle arrest in G1/S transition and was not accompanied by signs of cell death. Conclusion Our results suggest that EMX2 may constitute a putative therapeutic target for GB treatment. Further studies are required to decipher the gene networks and transduction signals involved in EMX2’s effect on cell proliferation

In Vivo Identification of Solar Radiation-Responsive Gene Network: Role of the p38 Stress-Dependent Kinase

Solar radiation is one of the most common threats to the skin, with exposure eliciting a specific protective cellular response. To decrypt the underlying mechanism, we used whole genome microarrays (Agilent 44K) to study epidermis gene expression in vivo in skin exposed to simulated solar radiation (SSR). We procured epidermis samples from healthy Caucasian patients, with phototypes II or III, and used two different SSR doses (2 and 4 J/cm 2), the lower of which corresponded to the minimal erythemal dose. Analyses were carried out five hours after irradiation to identify early gene expression events in the photoprotective response. About 1.5 % of genes from the human genome showed significant changes in gene expression. The annotations of these affected genes were assessed. They indicated a strengthening of the inflammation process and up-regulation of the JAK-STAT pathway and other pathways. Parallel to the p53 pathway, the p38 stress-responsive pathway was affected, supporting and mediating p53 function. We used an ex vivo assay with a specific inhibitor of p38 (SB203580) to investigate genes the expression of which was associated with active p38 kinase. We identified new direct p38 target genes and further characterized the role of p38. Our findings provide further insight int

Light-Dependent Regulation of Cell Division in Ostreococcus: Evidence for a Major Transcriptional Input1[W]

Cell division often occurs at specific times of the day in animal and photosynthetic organisms. Studies in unicellular photosynthetic algae, such as Chlamydomonas or Euglena, have shown that the photoperiodic control of cell division is mediated through the circadian clock. However, the underlying mechanisms remain unknown. We have studied the molecular basis of light-dependent control of cell division in the unicellular green alga Ostreococcus. We found that cell division obeys a circadian oscillator in Ostreococcus. We provide evidence suggesting that the clock may, at least in part, regulate directly cell division independently of the metabolism. Combined microarray and quantitative real-time reverse transcription-polymerase chain reaction analysis of the main core cell cycle gene expression revealed an extensive transcriptional regulation of cell division by the photoperiod in Ostreococcus. Finally, transcription of the main core cell cycle genes, including cyclins and cyclin-dependent kinases, was shown to be under circadian control in Ostreococcus, suggesting that these genes are potential targets of the circadian clock in the control of cell division

NGS panel V1.1 for the routine deep sequencing-based diagnostic of somatic hotspot theranostic mutations on FFPE tumours: A prospective study of 500 cancer samples

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Genome-wide association study identifies TF as a significant modifier gene of iron metabolism in HFE hemochromatosis

International audienceBackground : Hereditary hemochromatosis (HH) is the most common form of genetic iron loading disease. It is mainly related to the HFE C282Y/C282Y homozygous genotype that is however a necessary but not a sufficient condition to develop clinical and even biochemical HH. This suggests that modifiers genes are likely involved in the expressivity of the disease. Our aim was to identify such modifier genes. Patients and methods : We performed a genome-wide association study (GWAS) using DNAs collected from 474 unrelated C282Y homozygotes. Associations were examined for both quantitative iron burden indices and clinical outcomes with 534,213 single nucleotide polymorphisms (SNP) genotypes, with replication analyses in an independent sample of 748 C282Y homozygotes from four different European centres. Results : One SNP met genome-wide statistical significance for association with transferrin concentration (rs3811647, GWAS p-value of 7×10−9 and replication p-value of 5×10−13). This SNP located within intron 11 of TF gene had pleiotropic effect on serum iron (GWAS p-value of 4.9×10−6 and replication p-value of 3.2×10−6). Both serum transferrin and iron levels were associated with serum ferritin levels, amount of iron removed and global clinical stage (p<0.01). Serum iron levels were also associated with fibrosis stage (p<0.0001). Conclusion : This GWAS, the largest one performed so far in unselected HFE-HH patients, identified the rs3811647 polymorphism in the TF gene as the only SNP significantly associated with iron metabolism through serum transferrin and iron levels. Because these two outcomes were clearly associated with the biochemical and clinical expression of the disease, an indirect link between the rs3811647 polymorphism and the phenotypic presentation of HFE-HH is likely