161 research outputs found

    Marker assisted selection of malic-consuming saccharomyces cerevisiae strains for winemaking. Efficiency and limits of a qtl’s driven breeding program

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    Natural Saccharomyces cerevisiae yeast strains exhibit very large genotypic and phenotypic diversity. Breeding programs that take advantage of this characteristic are widely used for selecting starters for wine industry, especially in the recent years when winemakers need to adapt their production to climate change. The aim of this work was to evaluate a marker assisted selection (MAS) program to improve malic acid consumption capacity of Saccharomyces cerevisiae in grape juice. Optimal individuals of two unrelated F1-hybrids were crossed to get a new genetic background carrying many « malic consumer » loci. Then, eleven quantitative trait loci (QTLs) already identified were used for implementing the MAS breeding program. By this method, extreme individuals able to consume more than 70% of malic acid in grape juice were selected. These individuals were tested in different enological matrixes and compared to their original parental strains. They greatly reduced the malic acid content at the end of alcoholic fermentation, they appeared to be robust to the environment, and they accelerated the ongoing of malolactic fermentations by Oenococcus oeni. This study illustrates how MAS can be efficiently used for selecting industrial Saccharomyces cerevisiae strains with outlier properties for winemaking.Centre français de phĂ©nomique vĂ©gĂ©talePlateforme d'Innovation " ForĂȘt-Bois-Fibre-Biomasse du Futur

    SSU1 Checkup, a Rapid Tool for Detecting Chromosomal Rearrangements Related to the SSU1 Promoter in Saccharomyces cerevisiae: An Ecological and Technological Study on Wine Yeast

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    Chromosomal rearrangements (CR) such as translocations, duplications and inversions play a decisive role in the adaptation of microorganisms to specific environments. In enological Saccharomyces cerevisiae strains, CR involving the promoter region of the gene SSU1 lead to a higher sulfite tolerance by enhancing the SO2 efflux. To date, three different SSU1 associated CR events have been described, including translocations XV-t-XVI and VIII-t-XVI and inversion inv-XVI. In the present study, we developed a multiplex PCR method (SSU1 checkup) that allows a rapid characterization of these three chromosomal configurations in a single experiment. Nearly 600 S. cerevisiae strains collected from fermented grape juice were genotyped by microsatellite markers. We demonstrated that alleles of the SSU1 promoter are differently distributed according to the wine environment (cellar versus vineyard) and the nature of the grape juice. Moreover, rearranged SSU1 promoters are significantly enriched among commercial starters. In addition, the analysis of nearly isogenic strains collected in wine related environments demonstrated that the inheritance of these CR shapes the genetic diversity of clonal populations. Finally, the link between the nature of SSU1 promoter and the tolerance to sulfite was statistically validated in natural grape juice containing various SO2 concentrations. The SSU1 checkup is therefore a convenient new tool for addressing population genetics questions and for selecting yeast strains by using molecular markers.Fil: Marullo, Philippe. Universite de Bordeaux; FranciaFil: Claisse, Olivier. Universite de Bordeaux; FranciaFil: Raymond Eder, María Laura. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Börlin, Marine. Universite de Bordeaux; FranciaFil: Feghali, Nadine. Lebanese University; LíbanoFil: Bernard, Margaux. Universite de Bordeaux; FranciaFil: Legras, Jean Luc. Université Montpellier II; FranciaFil: Albertin, Warren. Universite de Bordeaux; FranciaFil: Rosa, Alberto Luis. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Masneuf Pomarede, Isabelle. Universite de Bordeaux; Franci

    Agroécologie:utopie ou vision d'avenir?

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    l’heure oĂč l’agroĂ©cologie devient un concept incontournable dans la sphĂšre publique, elle reste encore une notion nĂ©buleuse aux interprĂ©tations multiples. Incontour-nable, au point que nombres d’acteurs s’en emparent, empreint d’idĂ©alisme pour certains, d’opportunitĂ© politique ou d’aviditĂ© mercantile pour d’autres. NĂ©buleuse, car certains aspects restent encore peu Ă©tudiĂ©s comme son rĂŽle rĂ©el dans l’attĂ©nuation du changement climatique, sa contribution, difficile Ă  caractĂ©riser, en terme de services Ă  la sociĂ©tĂ©, comme les services Ă©cosystĂ©-miques, le bien-ĂȘtre et la qualitĂ© de vie pour les citoyen·ne·s et les paysan·ne·s en particulier ou enfin son lien intrinsĂšque avec la lutte pour l’égalitĂ© de genre. Ce numĂ©ro nous amĂšne ainsi Ă  une comprĂ©hension plus profonde et une vision plus systĂ©mique de ce que recĂšle l’agroĂ©cologie

    Front Microbiol

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    Chromosomal rearrangements (CR) such as translocations, duplications and inversions play a decisive role in the adaptation of microorganisms to specific environments. In enological strains, CR involving the promoter region of the gene lead to a higher sulfite tolerance by enhancing the SO efflux. To date, three different associated CR events have been described, including translocations XV-t-XVI and VIII-t-XVI and inversion inv-XVI. In the present study, we developed a multiplex PCR method ( checkup) that allows a rapid characterization of these three chromosomal configurations in a single experiment. Nearly 600 strains collected from fermented grape juice were genotyped by microsatellite markers. We demonstrated that alleles of the promoter are differently distributed according to the wine environment (cellar versus vineyard) and the nature of the grape juice. Moreover, rearranged promoters are significantly enriched among commercial starters. In addition, the analysis of nearly isogenic strains collected in wine related environments demonstrated that the inheritance of these CR shapes the genetic diversity of clonal populations. Finally, the link between the nature of promoter and the tolerance to sulfite was statistically validated in natural grape juice containing various SO concentrations. The checkup is therefore a convenient new tool for addressing population genetics questions and for selecting yeast strains by using molecular markers

    Identification of CT radiomic features robust to acquisition and segmentation variations for improved prediction of radiotherapy-treated lung cancer patient recurrence.

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    peer reviewedThe primary objective of the present study was to identify a subset of radiomic features extracted from primary tumor imaged by computed tomography of early-stage non-small cell lung cancer patients, which remain unaffected by variations in segmentation quality and in computed tomography image acquisition protocol. The robustness of these features to segmentation variations was assessed by analyzing the correlation of feature values extracted from lesion volumes delineated by two annotators. The robustness to variations in acquisition protocol was evaluated by examining the correlation of features extracted from high-dose and low-dose computed tomography scans, both of which were acquired for each patient as part of the stereotactic body radiotherapy planning process. Among 106 radiomic features considered, 21 were identified as robust. An analysis including univariate and multivariate assessments was subsequently conducted to estimate the predictive performance of these robust features on the outcome of early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy. The univariate predictive analysis revealed that robust features demonstrated superior predictive potential compared to non-robust features. The multivariate analysis indicated that linear regression models built with robust features displayed greater generalization capabilities by outperforming other models in predicting the outcomes of an external validation dataset

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Carbone des sols en Afrique

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    Les sols sont une ressource essentielle Ă  prĂ©server pour la production d’aliments, de fibres, de biomasse, pour la filtration de l’eau, la prĂ©servation de la biodiversitĂ© et le stockage du carbone. En tant que rĂ©servoirs de carbone, les sols sont par ailleurs appelĂ©s Ă  jouer un rĂŽle primordial dans la lutte contre l’augmentation de la concentration de gaz Ă  effet de serre. Ils sont ainsi au centre des objectifs de dĂ©veloppement durable (ODD) des Nations unies, notamment les ODD 2 « Faim zĂ©ro », 13 « Lutte contre le changement climatique », 15 « Vie terrestre », 12 « Consommation et production responsables » ou encore 1 « Pas de pauvretĂ© ». Cet ouvrage prĂ©sente un Ă©tat des lieux des sols africains dans toute leur diversitĂ©, mais au-delĂ , il documente les capacitĂ©s de stockage de carbone selon les types de sols et leurs usages en Afrique. Il propose Ă©galement des recommandations autour de l’acquisition et de l’interprĂ©tation des donnĂ©es, ainsi que des options pour prĂ©server, voire augmenter les stocks de carbone dans les sols. Tous les chercheurs et acteurs du dĂ©veloppement impliquĂ©s dans les recherches sur le rĂŽle du carbone des sols sont concernĂ©s par cette synthĂšse collective. Fruit d’une collaboration entre chercheurs africains et europĂ©ens, ce livre insiste sur la nĂ©cessitĂ© de prendre en compte la grande variĂ©tĂ© des contextes agricoles et forestiers africains pour amĂ©liorer nos connaissances sur les capacitĂ©s de stockage de carbone des sols et lutter contre le changement climatique

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

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    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

    The axon guidance receptor ROBO4, a major player of the osteotropism of metastatic breast cancer cells

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    Les taux de guĂ©rison du cancer du sein sont en progression constante, toutefois l’apparition de mĂ©tastases osseuses contribue Ă  la morbiditĂ© et Ă  la mortalitĂ© des femmes Ă  un stade avancĂ© et les traitements actuels ne sont que palliatifs. Afin de prĂ©venir les mĂ©tastases osseuses, il est essentiel de mieux comprendre les mĂ©canismes molĂ©culaires qui contrĂŽlent les Ă©vĂ©nements cellulaires prĂ©cĂ©dant l'apparition de lĂ©sions squelettiques. Dans ce but, une analyse transcriptomique comparative a Ă©tĂ© rĂ©alisĂ©e entre une lignĂ©e de cellules de cancer du sein humaines MDA-MB-231 qui dissĂ©mine dans plusieurs organes sans site prĂ©fĂ©rentiel, et une sous-population ostĂ©otropique, les cellules B02, qui mĂ©tastasent uniquement dans les os. Par comparaison Ă  la lignĂ©e MDA-MB-231, les cellules B02 surexpriment Roundabout 4 (ROBO4), codant un rĂ©cepteur cellulaire membranaire, appartenant Ă  la famille des rĂ©cepteurs de guidage axonal Roundabout. Physiologiquement, ROBO4 est impliquĂ© dans l'angiogenĂšse, l'intĂ©gritĂ© des vaisseaux sanguins et la migration des cellules souches hĂ©matopoĂŻĂ©tiques dans la niche ostĂ©oblastique. Afin de dĂ©terminer si ROBO4 peut, Ă©galement, jouer un rĂŽle de mĂ©diateur dans la localisation des cellules tumorales au sein de la moelle osseuse, nous avons invalidĂ© ROBO4 dans les cellules B02 en utilisant une stratĂ©gie CRISPR / Cas9. In vivo, l'injection orthotopique de cellules B02 KO ROBO4 a entraĂźnĂ© la formation de tumeurs plus petites par rapport Ă  celles formĂ©es par les cellules B02. De mĂȘme, dans les os, on observe une forte diminution de la croissance tumorale et de l’étendue de l’ostĂ©olyse. Des protocoles Ă  court-terme de formation de micro-mĂ©tastases ont Ă©galement montrĂ© un rĂŽle de ROBO4 dans les Ă©tapes prĂ©coces de la colonisation osseuse, probablement en agissant sur l'ancrage et/ou la survie des cellules tumorales. De plus, la colonisation d’une niche ostĂ©oblastique humanisĂ©e implantĂ©e en sous-cutanĂ©e chez des souris NOD / SCID, par les cellules B02 KO ROBO4 a Ă©galement Ă©tĂ© nettement rĂ©duite en comparaison aux cellules B02. Par consĂ©quent, ROBO4 intervient dans la dissĂ©mination osseuse prĂ©coce de cellules cancĂ©reuses du sein et dans la formation tumorale. In vitro, l’interaction des cellules B02 KO ROBO4 avec les cellules rĂ©sidentes de la moelle osseuse est rĂ©duite par rapport Ă  celle observĂ©e avec les cellules parentales B02. Les co-cultures de cellules B02 ou B02 KO ROBO4 en suspension avec les cellules de la moelle osseuse, conduisent Ă  la formation de mammosphĂšres hĂ©tĂ©rotypiques. Cependant, leurs tailles sont considĂ©rablement rĂ©duites suite Ă  l'inhibition de ROBO4. Des rĂ©sultats similaires sont observĂ©s lors de la culture homotypique de cellules B02 ou B02 KO ROBO4. On observe Ă©galement une importante rĂ©duction de l’agrĂ©gation cellulaire lorsque ROBO4 est inhibĂ©e, suggĂ©rant un rĂŽle de ROBO4 dans l’interaction cellulaire. De plus, les cellules B02 KO ROBO4 sont plus petites et plus isolĂ©es que les cellules B02 parentales, comme le montre l'analyse du cytosquelette d'actine. Ces rĂ©sultats nous permettent d’émettre l’hypothĂšse que ROBO4 est une molĂ©cule d’adhĂ©rence jouant un rĂŽle important dans la cohĂ©sion des cellules tumorales et dans l’interaction des cellules cancĂ©reuses avec les cellules du microenvironnement osseux. De façon intĂ©ressante, l’inhibition de ROBO4, par utilisation d’un anticorps anti-ROBO4, rĂ©duit Ă©galement la formation de sphĂ©roĂŻdes et la colonisation osseuse des cellules B02. L’ensemble de ces rĂ©sultats suggĂšrent que ROBO4 pourrait ĂȘtre une nouvelle cible thĂ©rapeutique dans le traitement de tumeur primitive du sein et des mĂ©tastases osseusesThe cure rates of breast cancer are steadily increasing; however, the occurrence of bone metastases contributes to the morbidity and mortality of women at an advanced stage and current treatments are only palliative. In order to prevent bone metastasis, it is vital to increase our understanding of the molecular mechanisms that control cellular events preceding the development of overt skeletal lesions. A comparative transcriptional analysis was performed between human MDA-MB-231 breast cancer cells that spread to several organs in animals, and a sub-population of the MDA-MB-231 cell line (B02) that metastasis only to bones. Compared to MDA-MB-231, B02 cells overexpress Roundabout 4 (ROBO4), encoding a cell surface receptor belonging to the Roundabout family of axonal guidance receptors. ROBO4 is involved in angiogenesis, blood vessel integrity and homing of hematopoietic stem cells in the osteoblastic niche. To determine whether ROBO4 could also mediate the homing of tumour cells in the bone marrow, we invalidate ROBO4 in B02 cells using a CRISPR/Cas9 strategy (KO ROBO4 B02). In vivo, orthotopic injection of KO ROBO4 B02 cells leads to smaller primary tumours compared to the ones formed by B02 control cell line. Moreover, in bone, ROBO4 invalidation induces a strong decrease of tumour growth, osteolysis occurrence and micrometastasis formation. Short-term protocols show the involvement of ROBO4 in the early-step of bone colonisation, probably by acting in tumour cell anchorage and/or survival. Furthermore, compared to B02 cells, the homing of KO ROBO4 B02 cells in a humanized osteoblastic niche implanted subcutaneously in NOD/SCID mice is also markedly reduced. Therefore, ROBO4 is involved in the early bone marrow dissemination of breast cancer cells and in tumor formation. According to this result, in vitro, the interaction of KO ROBO4 B02 cells with bone marrow resident cells is decreased, compared to what is observe with parental B02 cells. After the co-culture of B02 or KO ROBO4 cells in suspension with bone marrow resident cells, they both form heterotypic mammospheres. However, their size is substantially reduced in the absence of ROBO4. Similar findings were observed in homotypic culture of B02 or KO ROBO4 cells. An important decrease of tumor cell aggregation is also observed when ROBO4 is inhibited, suggesting a role of ROBO4 in cell interaction. Moreover, KO ROBO4 B02 cells are smaller and more isolated than parental B02 cells, as shown in actin cytoskeletal analysis. Altogether, these results provide strong evidence that ROBO4 is an adherent molecule which plays a crucial role in tumour cell cohesion and in the interaction of cancer cells with bone cells component. Interestingly, ROBO4 inhibition, using an anti-ROBO4 antibody, also reduces spheroid formation and bone colonization of B02 cells. Taken together, these results suggest ROBO4 as a new potential therapeutic target to treat primary breast tumours and bone metastasi
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