SNP discovery and genetic mapping using genotyping by sequencing of whole genome genomic DNA from a pea RIL population

International audienceBackground - Progress in genetics and breeding in pea still suffers from the limited availability of molecular resources. SNP markers that can be identified through affordable sequencing processes, without the need for prior genome reduction or a reference genome to assemble sequencing data would allow the discovery and genetic mapping of thousands of molecular markers. Such an approach could significantly speed up genetic studies and marker assisted breeding for non-model species. Results - A total of 419,024 SNPs were discovered using HiSeq whole genome sequencing of four pea lines, followed by direct identification of SNP markers without assembly using the discoSnp tool. Subsequent filtering led to the identification of 131,850 highly designable SNPs, polymorphic between at least two of the four pea lines. A subset of 64,754 SNPs was called and genotyped by short read sequencing on a subpopulation of 48 RILs from the cross 'Baccara' x 'PI180693'. This data was used to construct a WGGBS-derived pea genetic map comprising 64,263 markers. This map is collinear with previous pea consensus maps and therefore with the Medicago truncatula genome. Sequencing of four additional pea lines showed that 33 % to 64 % of the mapped SNPs, depending on the pairs of lines considered, are polymorphic and can therefore be useful in other crosses. The subsequent genotyping of a subset of 1000 SNPs, chosen for their mapping positions using a KASP™ assay, showed that almost all generated SNPs are highly designable and that most (95 %) deliver highly qualitative genotyping results. Using rather low sequencing coverages in SNP discovery and in SNP inferring did not hinder the identification of hundreds of thousands of high quality SNPs. Conclusions - The development and optimization of appropriate tools in SNP discovery and genetic mapping have allowed us to make available a massive new genomic resource in pea. It will be useful for both fine mapping within chosen QTL confidence intervals and marker assisted breeding for important traits in pea improvement

Use of sultines in the asymmetric synthesis of polypropionate antibiotics

At low temperature and in the presence of an acid catalyst, SO2 adds to 1,3-dienes equilibrating with the corresponding 3,6-dihydro-1,2-oxathiin-2-oxides (sultines). These compounds are unstable above -60 degrees C and equilibrate with the more stable 2,5-dihydrothiophene 1,1-dioxides (sulfolenes). The hetero-Diels-Alder additions of SO2 are suprafacial and follow the Alder endo rule. The sultines derived from 1-oxy-substituted and 1,3-dioxy-disubstituted 1,3-dienes cannot be observed at -100 degrees C but are believed to be formed faster than the corresponding sulfolenes. In the presence of acid catalysts, the 6-oxy-substituted sultines equilibrate with zwitterionic species that react with electron-rich alkenes such as enoxysilanes and allylsilanes, generating beta,gamma-unsaturated silyl sulfinates that can be desilylated and desulfinylated to generate polypropionate fragments containing up to three contiguous stereogenic centers and an (E)-alkene unit. Alternatively, the silyl sulfinates can be reacted with electrophiles to generate polyfunctional sulfones (one-pot, four-component synthesis of sulfones), or oxidized into sulfonyl chlorides and reacted with amines, then realizing a one-pot, four-component synthesis of polyfunctional sulfonamides. Using enantiomerically enriched dienes such as 1-[(R)- or 1-(S)-phenylethyloxyl-2-methyl-(E,E)-penta-1,3-dien-3-yl isobutyrate, derived from inexpensive (R)- or (S)-1-phenylethanol, enantiomerically enriched stereotriads are obtained in one-pot operations. The latter are ready for further chain elongation. This has permitted the development of expeditious total asymmetric syntheses of important natural products of biological interest such as the baconipyrones, rifamycin S, and apoptolidin A

CXCR4 Expression in Prostate Cancer Progenitor Cells

Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44+/CD133+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy

The future of biotic indices in the ecogenomic era: Integrating (e)DNA metabarcoding in biological assessment of aquatic ecosystems

The bioassessment of aquatic ecosystems is currently based on various biotic indices that use the occurrence and/or abundance of selected taxonomic groups to define ecological status. These conventional indices have some limitations, often related to difficulties in morphological identification of bioindicator taxa. Recent development of DNA barcoding and metabarcoding could potentially alleviate some of these limitations, by using DNA sequences instead of morphology to identify organisms and to characterize a given ecosystem. In this paper, we review the structure of conventional biotic indices, and we present the results of pilot metabarcoding studies using environmental DNA to infer biotic indices. We discuss the main advantages and pitfalls of metabarcoding approaches to assess parameters such as richness, abundance, taxonomic composition and species ecological values, to be used for calculation of biotic indices. We present some future developments to fully exploit the potential of metabarcoding data and improve the accuracy and precision of their analysis. We also propose some recommendations for the future integration of DNA metabarcoding to routine biomonitoring programs.info:eu-repo/semantics/publishedVersio

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Sulfur dioxide mediated syntheses of polyene containing natural products

The goal of this thesis was to open a new route to the synthesis of conjugated trienes using a new SO2-based C-C bond forming reactions developed in Lausanne. In addition, the potential of SO2 for applications in synthetic organic chemistry has been exploited. Firstly, we discovered that under suitable conditions sulfur dioxide is able to undergo ene reaction with different building blocks such as enoxysilanes and allylsilanes to form the corresponding sulfinates. The latter can be used as key intermediates for the preparation of β-ketones, β-keto-sulfonamides and β-keto-sulfonic esters. This approach allows preparing β-keto-sulfonamides in one-pot operations. Up to now, the same type of compounds would require multi-steps syntheses. Considering the importance of sulfonamides and sulfonic esters in medicinal chemistry we prepared representative examples of such compounds. Secondly, our studies demonstrate, for the first time, that sulfones containing (E)-alkene units can be obtained through the reaction of (E,E)-1-silyloxy-2-methylpenta-1,3-diene with substituted enoxysilanes and an excess of sulfur dioxide, followed by subsequent quenching with electrophiles. Importantly, this four-component reaction yields (E)-alkenes only in the presence of a protic acid promoter and only with 1-silyloxypentadienes. In all cases mixtures of α,β-syn and α,β-anti ketones are obtained. The α,β-diastereoselectivity of the oxyallylation (face selectivity of the enoxysilane addition) does not surpass 6:1 (3R,4S vs.3S,4S). Interestingly only β,ε-like substituted ε-sulfonylketones are formed, in contrast with the (Z)-isomers which present unlike β,ε-relative configuration. Thirdly, sulfur dioxide-based chemistry was applied for the asymmetric synthesis of the conjugated (E,E,E)-triene moiety of apoptolidinone, a highly potent apoptosis inducing agent with a daunting molecular architecture. Two main synthetic routes towards the synthesis of the trienic fragment of apoptolidinone were developed, one leading to the racemic fragment and a second route leading to the enantiomerically enriched C(1)-C(9) fragment. The latter was transformed further into the fragment already synthesized by Nicolaou and co-workers, demonstrating that this second route is significantly shorter than the route previously reported in the literature. The same methodology yields also facile access to the trienic part C(5)-C(14) fragment of restricticin. This underlines further the general applicability and the high flexibilities of our method toward the synthesis of trienes

Synthesis of a Series of Promising Isobenzofurans for the Reduction of Acute Mucositis Risk after Chemo- and Radiotherapy.

Mycophenolate mofelite (MMF), an immunosuppressant and prodrug of mycophenolic acid (MPA), is used extensively in transplant medicine and more specifically after bone marrow transplantation to prevent acute rejection and other severe complications such as mucositis. Despite extensive research, a mucositis-specific pain treatment has yet to be developed in order to improve the conditions of patients treated by chemo- and radiotherapy. Herein, we present the synthesis of a small series of isobenzofuran analogues identified during a screening campaign as possible mucositis mediators

La publicité des avis du Conseil d’État sur les projets de loi du Gouvernement

participation à la table rondeNational audienc

La publicité des avis du Conseil d’État sur les projets de loi du Gouvernement

participation à la table rondeNational audienc

La publicité des avis du Conseil d’État sur les projets de loi du Gouvernement

participation à la table rondeNational audienc