Hydrodynamique du plateau continental aquitain et influence sur les épisodes à Dinophysis dans le Bassin d'Arcachon

Des épisodes à Dinophysis affectent périodiquement l'exploitation des fruits de mer dans le Bassin d'Arcachon. Le réseau de surveillance interne au Bassin d'Arcachon montre que Dinophysis est advecté de l'océan ouvert. Le but de cette étude est de déterminer l'origine de Dinophysis. Des campagnes en mer sur le plateau continental Aquitain ont permis d'identifier une zone propice au développement de Dinophysis au large de Capbreton. Les épisodes à Dinophysis dans le bassin d'Arcachon se produisent suite à des vents d'Ouest qui induisent des courants vers le Sud d'après la littérature. L'étude des données hydrodynamiques acquises pendant les campagnes met en évidence un processus complexe et nouveau suite aux vents d'Ouest: de forts courants le long de la côte vers le Nord capables de transporter Dinophysis de Capbreton jusqu'au Bassin d'Arcachon. Un travail de modélisation a permis de reproduire ce courant et d'étudier son mécanisme particulier lié coin Sud-Est du Golfe de Gascogne.AbstractBORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Evaluation of methods for amplification of picogram amounts of total RNA for whole genome expression profiling

<p>Abstract</p> <p>Background</p> <p>For more than a decade, microarrays have been a powerful and widely used tool to explore the transcriptome of biological systems. However, the amount of biological material from cell sorting or laser capture microdissection is much too small to perform microarray studies. To address this issue, RNA amplification methods have been developed to generate sufficient targets from picogram amounts of total RNA to perform microarray hybridisation.</p> <p>Results</p> <p>In this study, four commercial protocols for amplification of picograms amounts of input RNA for microarray expression profiling were evaluated and compared. The quantitative and qualitative performances of the methods were assessed. Microarrays were hybridised with the amplified targets and the amplification protocols were compared with respect to the quality of expression profiles, reproducibility within a concentration range of input RNA, and sensitivity. The results demonstrate significant differences between these four methods.</p> <p>Conclusion</p> <p>In our hands, the WT-Ovation pico system proposed by Nugen appears to be the most suitable for RNA amplification. This comparative study will be useful to scientists needing to choose an amplification method to carry out microarray experiments involving samples comprising only a few cells and generating picogram amounts of RNA.</p

Axial dipolar dynamo action in the Taylor-Green vortex

We present a numerical study of the magnetic field generated by the Taylor-Green vortex. We show that periodic boundary conditions can be used to mimic realistic boundary conditions by prescribing the symmetries of the velocity and magnetic fields. This gives insight in some problems of central interest for dynamos: the possible effect of velocity fluctuations on the dynamo threshold, the role of boundary conditions on the threshold and on the geometry of the magnetic field generated by dynamo action. In particular, we show that an axial dipolar dynamo similar to the one observed in a recent experiment can be obtained with an appropriate choice of the symmetries of the magnetic field. The nonlinear saturation is studied and a simple model explaining the magnetic Prandtl number dependence of the super/sub critical nature of the dynamo transition is given

Standardized whole-blood transcriptional profiling enables the deconvolution of complex induced immune responses

Figura como autor también el Milieu Intérieur ConsortiumSystems approaches for the study of immune signaling pathways have been traditionally based on purified cells or cultured lines. However, in vivo responses involve the coordinated action of multiple cell types, which interact to establish an inflammatory microenvironment. We employed standardized whole-blood stimulation systems to test the hypothesis that responses to Toll-like receptor ligands or whole microbes can be defined by the transcriptional signatures of key cytokines. We found 44 genes, identified using Support Vector Machine learning, that captured the diversity of complex innate immune responses with improved segregation between distinct stimuli. Furthermore, we used donor variability to identify shared inter-cellular pathways and trace cytokine loops involved in gene expression. This provides strategies for dimension reduction of large datasets and deconvolution of innate immune responses applicable for characterizing immunomodulatory molecules. Moreover, we provide an interactive R-Shiny application with healthy donor reference values for induced inflammatory genes

Spring-neap tidal and circadian variability in the distribution of two groups of Pseudo-nitzschia species in an upwelling influenced estuary

High-resolution physical and biological measurements were carried out in the Ría de Pontevedra (NW Spain) in late spring during the ‘HABIT Pontevedra 2007’ survey, which utilized high vertical resolution instruments. Cell maxima of P. delicatissima (6 x 105 cells L-1) and P. seriata (2 x 106 cells L-1) groups were observed during the first half of the cruise during downwelling and a significant decrease in cell numbers occurred during subsequent upwelling conditions. The effect of tidal (both semidiurnal and spring-neap) and event driven (upwelling-downwelling cycle) variability were evident. The observed sequence of events suggests that Pseudo-nitzschia populations were advected from the shelf. The circadian variability was regulated by tidal forcing and Pseudo-nitzschia spp. maxima were observed at low tide. From results presented here we conclude that the magnitude of spring-neap tidal and circadian variability has to be considered when designing and implementing harmful algal bloom monitoring programmesEn prens

HRAS is a therapeutic target in malignant chemo-resistant adenomyoepithelioma of the breast

Abstract Malignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours’ samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors

Marine harmful algal blooms, human health and wellbeing : challenges and opportunities in the 21st century

Author Posting. © Marine Biological Association of the United Kingdom, 2015. This is the author's version of the work. It is posted here by permission of Marine Biological Association of the United Kingdom for personal use, not for redistribution. The definitive version was published in Journal of the Marine Biological Association of the United Kingdom 96 (2016): 61-91, doi:10.1017/S0025315415001733.Microalgal blooms are a natural part of the seasonal cycle of photosynthetic organisms in marine ecosystems. They are key components of the structure and dynamics of the oceans and thus sustain the benefits that humans obtain from these aquatic environments. However, some microalgal blooms can cause harm to humans and other organisms. These harmful algal blooms (HABs) have direct impacts on human health and negative influences on human wellbeing, mainly through their consequences to coastal ecosystem services (valued fisheries, tourism and recreation) and other marine organisms and environments. HABs are natural phenomena, but these events can be favoured by anthropogenic pressures in coastal areas. Global warming and associated changes in the oceans could affect HAB occurrences and toxicity as well, although forecasting the possible trends is still speculative and requires intensive multidisciplinary research. At the beginning of the 21st century, with expanding human populations, particularly in coastal and developing countries, there is an urgent need to prevent and mitigate HABs’ impacts on human health and wellbeing. The available tools to address this global challenge include maintaining intensive, multidisciplinary and collaborative scientific research, and strengthening the coordination with stakeholders, policymakers and the general public. Here we provide an overview of different aspects to understand the relevance of the HABs phenomena, an important element of the intrinsic links between oceans and human health and wellbeing.The research was funded in part by the UK Medical Research Council (MRC) and UK Natural Environment Research Council (NERC) for the MEDMI Project; the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Environmental Change and Health at the London School of Hygiene and Tropical Medicine in partnership with Public Health England (PHE), and in collaboration with the University of Exeter, University College London and the Met Office; and the European Regional Development Fund Programme and European Social Fund Convergence Programme for Cornwall and the Isles of Scilly (University of Exeter Medical School). EB was supported by the CTM2014-53818-R project, from the Spanish Government (MINECO). KDA was in receipt of funding from the BBSRC-NERC research programme for multidisciplinary studies in sustainable aquaculture: health, disease and the environment. P. Hess was supported by Ifremer (RISALTOX) and the Regional Council of the Pays de la Loire (COSELMAR). Porter Hoagland was supported by the US National Science Foundation under NSF/CNH grant no. 1009106.2016-05-2

The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist

The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other’s TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes

Rapid Enzyme-linked Immunosorbent Assay for Detection of the Algal Toxin Domoic Acid

Domoic acid (DA) is a potent toxin produced by bloom-forming phytoplankton in the genus Pseudo-nitzschia, which is responsible for causing amnesic shellfish poisoning (ASP) in humans. ASP symptoms include vomiting, diarrhea, and in more severe cases confusion, loss of memory, disorientation, and even coma or death. This paper describes the development and validation of a rapid, sensitive, enzyme linked immunosorbent assay test kit for detecting DA using a monoclonal antibody. The assay gives equivalent results to those obtained using standard high performance liquid chromatography, fluorenylmethoxycarbonyl high performance liquid chromatography, or liquid chromatography—mass spectrometry methods. It has a linear range from 0.1–3 ppb and was used successfully to measure DA in razor clams, mussels, scallops, and phytoplankton. The assay requires approximately 1.5 h to complete and has a standard 96-well format where each strip of eight wells is removable and can be stored at 4°C until needed. The first two wells of each strip serve as an internal control eliminating the need to run a standard curve. This allows as few as 3 or as many as 36 duplicate samples to be run at a time enabling real-time sample processing and limiting degradation of DA, which can occur during storage. There was minimal cross-reactivity in this assay with glutamine, glutamic acid, kainic acid, epi- or iso-DA. This accurate, rapid, cost-effective, assay offers environmental managers and public health officials an effective tool for monitoring DA concentrations in environment samples

A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts

Patients with follicular lymphoma (FL) have heterogeneous outcomes. Predictor models able to distinguish, at diagnosis, patients at high versus low risk of progression are still needed. A training set of fresh-frozen tumour biopsies was prospectively obtained from 160 untreated patients with high-tumour-burden follicular lymphoma enrolled in the phase 3 randomised PRIMA trial, in which rituximab maintenance was evaluated after rituximab plus chemotherapy induction (median follow-up 6·6 years [IQR 6·0-7·0]). RNA of sufficient quality was obtained for 149 of 160 cases, and Affymetrix U133 Plus 2.0 microarrays were used for gene-expression profiling. We did a multivariate Cox regression analysis to identify genes with expression levels associated with progression-free survival independently of maintenance treatment in a subgroup of 134 randomised patients. Expression levels from 95 curated genes were then determined by digital expression profiling (NanoString technology) in 53 formalin-fixed paraffin-embedded samples of the training set to compare the technical reproducibility of expression levels for each gene between technologies. Genes with high correlation (>0·75) were included in an L2-penalised Cox model adjusted on rituximab maintenance to build a predictive score for progression-free survival. The model was validated using NanoString technology to digitally quantify gene expression in 488 formalin-fixed, paraffin-embedded samples from three independent international patient cohorts from the PRIMA trial (n=178; distinct from the training cohort), the University of Iowa/Mayo Clinic Lymphoma SPORE project (n=201), and the Barcelona Hospital Clinic (n=109). All tissue samples consisted of pretreatment diagnostic biopsies and were confirmed as follicular lymphoma grade 1-3a. The patients were all treated with regimens containing rituximab and chemotherapy, possibly followed by either rituximab maintenance or ibritumomab-tiuxetan consolidation. We determined an optimum threshold on the score to predict patients at low risk and high risk of progression. The model, including the multigene score and the threshold, was initially evaluated in the three validation cohorts separately. The sensitivity and specificity of the score for the prediction of the risk of lymphoma progression at 2 years were assessed on the combined validation cohorts. FINDINGS: In the training cohort, the expression levels of 395 genes were associated with a risk of progression. 23 genes reflecting both B-cell biology and tumour microenvironment with correlation coefficients greater than 0·75 between the two technologies and sample types were retained to build a predictive model that identified a population at an increased risk of progression (p<0·0001). In a multivariate Cox model for progression-free survival adjusted on rituximab maintenance treatment and Follicular Lymphoma International Prognostic Index 1 (FLIPI-1) score, this predictor independently predicted progression (adjusted hazard ratio [aHR] of the high-risk group compared with the low-risk group 3·68, 95% CI 2·19-6·17 [p<0·0001]). The 5-year progression-free survival was 26% (95% CI 16-43) in the high-risk group and 73% (64-83) in the low-risk group. The predictor performances were confirmed in each of the individual validation cohorts (aHR comparing high-risk to low-risk groups 2·57 [95% CI 1·65-4·01] in cohort 1; 2·12 [1·32-3·39] in cohort 2; and 2·11 [1·01-4·41] in cohort 3). In the combined validation cohort, the median progression-free survival was 3·1 years (95% CI 2·4-4·8) in the high-risk group and 10·8 years (10·1-not reached) in the low-risk group (p<0·0001). The risk of lymphoma progression at 2 years was 38% (95% CI 29-46) in the high-risk group and 19% (15-24) in the low-risk group. In a multivariate analysis, the score predicted progression-free survival independently of anti-CD20 maintenance treatment and of the FLIPI score (aHR for the combined cohort 2·30, 95% CI 1·72-3·07). INTERPRETATION: We developed and validated a robust 23-gene expression-based predictor of progression-free survival that is applicable to routinely available formalin-fixed, paraffin-embedded tumour biopsies from patients with follicular lymphoma at time of diagnosis. Applying this score could allow individualised therapy for patients according to their risk category