The URGI plants and bio-agressors genomics annotation system

The URGI genomic annotation platform, developed in the framework of the GnpAnnot project, relies on well known GMOD tools (http://gmod.org): Apollo, Chado and GBrowse. Apollo is the graphical interface for visualization and annotation edition allowing curators to edit their genes according to evidences (transcript and protein similarity, comparative genomics). Manual annotations (gene curation validated/in progress) are saved in a dedicated Chado database and shared at the same time with other community annotations members. Validated genes/pseudogenes are then committed in the second Chado database accessible by GBrowse. (Résumé d'auteur

Risk of lung cancer mortality in nuclear workers from internal exposure to alpha particle-emitting radionuclides

BACKGROUND: Carcinogenic risks of internal exposures to alpha-emitters (except radon) are poorly understood. Since exposure to alpha particles-particularly through inhalation-occurs in a range of settings, understanding consequent risks is a public health priority. We aimed to quantify dose-response relationships between lung dose from alpha-emitters and lung cancer in nuclear workers. METHODS: We conducted a case-control study, nested within Belgian, French, and UK cohorts of uranium and plutonium workers. Cases were workers who died from lung cancer; one to three controls were matched to each. Lung doses from alpha-emitters were assessed using bioassay data. We estimated excess odds ratio (OR) of lung cancer per gray (Gy) of lung dose. RESULTS: The study comprised 553 cases and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean: 8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)-adjusted for external radiation, socioeconomic status, and smoking-was 11 (2.6, 24) for total alpha dose, 50 (17, 106) for plutonium, and 5.3 (-1.9, 18) for uranium. CONCLUSIONS: We found strong evidence for associations between low doses from alpha-emitters and lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though confidence intervals overlap. Risk estimates were similar to those estimated previously in plutonium workers, and in uranium miners exposed to radon and its progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are somewhat larger than but consistent with those for atomic bomb survivors.See video abstract at, http://links.lww.com/EDE/B232

MRI Findings in 77 Children with Non-Syndromic Autistic Disorder

International audienceBACKGROUND: The clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences. Our main objective was to evaluate the prevalence of brain abnormalities in a large group of children with a non-syndromic autistic disorder (AD) using T1, T2 and FLAIR MRI sequences. METHODOLOGY: MRI inspection of 77 children and adolescents with non-syndromic AD (mean age 7.4+/-3.6) was performed. All met the DSM-IV and ADI -R criteria for autism. Based on recommended clinical and biological screenings, we excluded patients with infectious, metabolic or genetic diseases, seizures or any other neurological symptoms. Identical MRI inspections of 77 children (mean age 7.0+/-4.2) without AD, developmental or neurological disorders were also performed. All MRIs were acquired with a 1.5-T Signa GE (3-D T1-FSPGR, T2, FLAIR coronal and axial sequences). Two neuroradiologists independently inspected cortical and sub-cortical regions. MRIs were reported to be normal, abnormal or uninterpretable. PRINCIPAL FINDINGS: MRIs were judged as uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69 patients), abnormalities were reported. Three predominant abnormalities were observed, including white matter signal abnormalities (19/69), major dilated Virchow-Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all, 52% of the MRIs were interpreted as normal (36/69 patients). CONCLUSIONS: An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in non-syndromic autism. These results could contribute to further etiopathogenetic research into autism

Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans expedition

A unique collection of oceanic samples was gathered by the Tara Oceans expeditions (2009-2013), targeting plankton organisms ranging from viruses to metazoans, and providing rich environmental context measurements. Thanks to recent advances in the field of genomics, extensive sequencing has been performed for a deep genomic analysis of this huge collection of samples. A strategy based on different approaches, such as metabarcoding, metagenomics, single-cell genomics and metatranscriptomics, has been chosen for analysis of size-fractionated plankton communities. Here, we provide detailed procedures applied for genomic data generation, from nucleic acids extraction to sequence production, and we describe registries of genomics datasets available at the European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these metadata to the experimental procedures applied for their generation will help the scientific community to access these data and facilitate their analysis. This paper complements other efforts to provide a full description of experiments and open science resources generated from the Tara Oceans project, further extending their value for the study of the world's planktonic ecosystems

Lung function and atherosclerosis: a cross-sectional study of multimorbidity in rural Uganda

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure. Methods: We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status. Results: Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (β = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT. Conclusions: Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa

Retinoic acid receptor α as a novel contributor to adrenal cortex structure and function through interactions with Wnt and Vegfa signalling

International audiencePrimary aldosteronism (PA) is the most frequent form of secondary arterial hypertension. Mutations in different genes increase aldosterone production in PA, but additional mechanisms may contribute to increased cell proliferation and aldosterone producing adenoma (APA) development. We performed transcriptome analysis in APA and identified retinoic acid receptor alpha (RARα) signaling as a central molecular network involved in nodule formation. To understand how RARα modulates adrenal structure and function, we explored the adrenal phenotype of male and female Rarα knockout mice. inactivation of Rarα in mice led to significant structural disorganization of the adrenal cortex in both sexes, with increased adrenal cortex size in female mice and increased cell proliferation in males. Abnormalities of vessel architecture and extracellular matrix were due to decreased Vegfa expression and modifications in extracellular matrix components. On the molecular level, Rarα inactivation leads to inhibition of non-canonical Wnt signaling, without affecting the canonical Wnt pathway nor PKA signaling. Our study suggests that Rarα contributes to the maintenance of normal adrenal cortex structure and cell proliferation, by modulating Wnt signaling. Dysregulation of this interaction may contribute to abnormal cell proliferation, creating a propitious environment for the emergence of specific driver mutations in PA. Primary aldosteronism (PA) is the most common and curable form of secondary arterial hypertension, with prevalence estimations of up to 10% of cases in referred hypertensive patients, 4% of patients in primary care 1,2 and 20% of patients with resistant hypertension 3,4. Rapid diagnosis and treatment are important to prevent severe cardiovas-cular consequences of long term aldosterone exposure, which are independent of blood pressure levels and are du

Genome annotation and report system : an integrated system for structural and functional genome annotation (P800)

Nowadays with the development of NGS, more and more genomes are sequenced, producing very large amount of data. However, annotations can't keep pace, introducing a lack between genome data and annotation releases. To face this challenge, the URGI (http://urgi.versailles.inra.fr) platform aims at providing tools to annotate entirely sequenced genome comprising: pipelines, databases and user-friendly interfaces to browse and query the data. We will focus here on complementary systems developed in the frame of GnpIS and GnpAnnot project: - The distributed annotation system allows the curation of gene structure. This system relies on the well known GMOD databases and interfaces (chado/GBrowse/Apollo). Curated data are available and shared by the consortium community as soon as they are committed in the database using the "pure JDBC'" direct communication protocol between Apollo and Chado. - The Genome Report System (GRS), written in Java, was developed to produce various and user-friendly Web reports. GRS uses structural and functional genomic data stored in Chado database in order to provide users with a comprehensive list of information including cross references related to a specific gene. GRS proposes also a Gene Ontology browser and an editing module (GRE) to allow manual functional annotation. - Quick and advanced search are processed respectively through GnpIS QuickSearch (http://urgi.versailles.inra.fr/gnpis) and Biomart (GMOD). We will present the integration of these tools in the frame of a fungal genome annotation. (Texte intégral