11 research outputs found

    Que rĂ©vĂšlent les parcours et les pratiques des enseignants en classe de français ? ÉlĂ©ments de rĂ©flexions sur les conflits cognitifs et mĂ©thodologiques face aux traditions didactiques

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    International audienc

    Miniaturization of an extraction protocol for the monitoring of pesticides and polar transformation products in biotic matrices

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    The authors sincerely thank the fish farmers and owners for granting access to their ponds. They are also grateful to Alain IurĂ©tig (sampling and pre-treatment, Univ. of Lorraine), Pamela Hartmeyer (pre-treatment, Univ. of Lorraine), Aisha Nunoo (extractions, Univ. of Lorraine/ISA), and Maud Dessein-Lepasteur (extractions and analysis, Univ. of Lorraine/ISA) for their work, as well as to Arnaud Chaumot and Laura Garnero from the Ecotoxicology Team of the UR RIVERLY (INRAE, Centre de Lyon-Villeurbanne) for providing chironomid larvae. They would also like to thank ABC Translation for proofreading the manuscript.International audienceMonitoring pesticides in the environment requires the use of sensitive analytical methods. However, existing methods are generally not suitable for analyzing small organisms, as they require large matrix masses. This study explores the development of a miniaturized extraction protocol for the monitoring of small organisms, based on only 30 mg of matrix. The miniaturized sample preparation was developed using fish and macroinvertebrate matrices. It allowed the characterization of 41 pesticides and transformation products (log P from −1.9 to 4.8) in small samples with LC-MS/MS, based on European guidelines (European Commission DG-SANTE, 2019). Quantification limits ranged from 3 to 460 ng g−1 dry weight (dw) for fish and from 0.1 to 356 ng g−1 dw for invertebrates, with most below 60 ng g−1 dw. Extraction rates ranged from 70% to 120% for 35 molecules in fish. Recoveries ranged from 70% to 120% for 37 molecules in macroinvertebrates. Inter-day precision was below 30% for 32 molecules at quantification limits. The method was successfully applied to 17 fish and 19 macroinvertebrates collected from two ponds of the French region of Dombes in November and May 2018, respectively. Both sample matrices were nearly always contaminated with benzamide, imidacloprid-desnitro, and prosulfocarb at respective concentrations of 42–237, 3, and 30–165 ng g−1 dw in fish, and 62–438, 2–6, and 15–29 ng g−1 dw in macroinvertebrates. Results show that this method is an effective tool for characterizing polar pesticides in small biotic samples

    Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53

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    International audienceB-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessment of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex ({greater than or equal to}3 abnormalities) in 73% of the patients and highly complex (>5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving MYC [t(MYC)] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six of the 34 patients (76%) exhibit MYC aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in TP53, MYD88, BCOR, MYC, SF3B1, SETD2, CHD2, CXCR4, and BCLAF1 The majority of B-PLL used the IGHV3 or IGHV4 subgroups (89%), and displayed significantly mutated IGHV genes (79%). We identified three distinct cytogenetic risk groups: low-risk (no MYC aberration), intermediate-risk (MYC aberration but no del17p), and high-risk (MYC aberration and del17p) (p=.0006). In vitro drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif (BET) inhibitor targeting MYC) was associated with significantly lower viability of B-PLL cells harboring a t(MYC). We conclude that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting MYC may be a useful treatment option in this disease

    Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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    BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old
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