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"Besse, Bernard"
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A FUT2 Gene Common Polymorphism Determines Resistance to Rotavirus A of the P8 Genotype
2014
Attachment to carbohydrates of the histo-blood group type of several human Rotavirus strains (RVA) has recently been described. Synthesis of these ligands requires a functional FUT2 enzyme, suggesting that FUT2 null homozygote (ie, nonsecretor) individuals may not be recognized by most human RVA strains. Whereas such individuals represent 20% of the control population, this retrospective study determined that none of 51 patients infected by P[8] rotavirus strains were nonsecretors. The lack of α1,2fucosylated carbohydrate motifs in the gut surface mucosa is thus associated with resistance to symptomatic infection and virus attachment to such motifs is essential to the infection process.
Journal Article
An NS5A single optimized method to determine genotype, subtype and resistance profiles of Hepatitis C strains
by
Ribeyrol, Olivier
,
Besse, Bernard
,
Bourgeois, Nathalie
in
Amplification
,
Antiviral Agents - pharmacology
,
Biology and life sciences
2017
The objective was to develop a method of HCV genome sequencing that allowed simultaneous genotyping and NS5A inhibitor resistance profiling. In order to validate the use of a unique RT-PCR for genotypes 1-5, 142 plasma samples from patients infected with HCV were analysed. The NS4B-NS5A partial region was successfully amplified and sequenced in all samples. In parallel, partial NS3 sequences were analyzed obtained for genotyping. Phylogenetic analysis showed concordance of genotypes and subtypes with a bootstrap >95% for each type cluster. NS5A resistance mutations were analyzed using the Geno2pheno [hcv] v0.92 tool and compared to the list of known Resistant Associated Substitutions recently published. In conclusion, this tool allows determination of HCV genotypes, subtypes and identification of NS5A resistance mutations. This single method can be used to detect pre-existing resistance mutations in NS5A before treatment and to check the emergence of resistant viruses while undergoing treatment in major HCV genotypes (G1-5) in the EU and the US.
Journal Article
A FUT2 gene common polymorphism determines resistance to rotavirus A of the P8 genotype
2014
Attachment to carbohydrates of the histo-blood group type of several human Rotavirus strains (RVA) has recently been described. Synthesis of these ligands requires a functional FUT2 enzyme, suggesting that FUT2 null homozygote (ie, nonsecretor) individuals may not be recognized by most human RVA strains. Whereas such individuals represent 20% of the control population, this retrospective study determined that none of 51 patients infected by P[8] rotavirus strains were nonsecretors. The lack of α1,2fucosylated carbohydrate motifs in the gut surface mucosa is thus associated with resistance to symptomatic infection and virus attachment to such motifs is essential to the infection process.Attachment to carbohydrates of the histo-blood group type of several human Rotavirus strains (RVA) has recently been described. Synthesis of these ligands requires a functional FUT2 enzyme, suggesting that FUT2 null homozygote (ie, nonsecretor) individuals may not be recognized by most human RVA strains. Whereas such individuals represent 20% of the control population, this retrospective study determined that none of 51 patients infected by P[8] rotavirus strains were nonsecretors. The lack of α1,2fucosylated carbohydrate motifs in the gut surface mucosa is thus associated with resistance to symptomatic infection and virus attachment to such motifs is essential to the infection process.
Journal Article
Influenza virus A subtype H1N1 is inhibited by methylated β-lactoglobulin
by
Billaudel, Sylviane
,
Haertlé, Thomas
,
Sitohy, Mahmoud
in
Agricultural sciences
,
anatomy and morphology
,
Animals
2010
Addition of methylated β-lactoglobulin (Met-BLG) in the medium of MDCK cell lines infected with influenza virus subtype H1N1 reduced hemagglutination activity (HA) in a concentration dependent manner. Antiviral activity of Met-BLG depended on its concentration, viral load, and duration of infection. Using 17 μg/ml of Met-BLG inhibited 50% of HA of H1N1 grown in MDCK cells at 1 MOI after 24 h incubation at 37°C and in 5% CO2. Extension of incubation time enhanced antiviral action since the same concentration of Met-BLG inhibited about 61% of viral activity after 48 h. This viral inhibition was accompanied by a protection of MDCK cells as observed by using neutral red or by direct microscope examination. Reduction of viral RNA replication upon the addition of Met-BLG (50 μg/ml) was observed by real time-PCR showing a reduction of viral log value of about 0·9. When viral stock solution was mixed with 25 μg/ml Met-BLG in absence of cell lines, the morphology and viability of virus particles were significantly affected as observed by electron microscopy, and the number of intact virus particles was reduced by roughly 65%.
Journal Article
Influenza virus A subtype H1N1 is inhibited by methylated b-lactoglobulin
2010
Addition of methylated b-lactoglobulin (Met-BLG) in the medium of MDCK cell lines infected with influenza virus subtype H1N1 reduced hemagglutination activity (HA) in a concentration dependent manner. Antiviral activity of Met-BLG depended on its concentration, viral load, and duration of infection. Using 17 kg/ml of Met-BLG inhibited 50% of HA of H1N1 grown in MDCK cells at 1 MOI after 24 h incubation at 37C and in 5% CO2. Extension of incubation time enhanced antiviral action since the same concentration of Met-BLG inhibited about 61% of viral activity after 48 h. This viral inhibition was accompanied by a protection of MDCK cells as observed by using neutral red or by direct microscope examination. Reduction of viral RNA replication upon the addition of Met-BLG (50 kg/ml) was observed by real time-PCR showing a reduction of viral log value of about 0.9. When viral stock solution was mixed with 25 kg/ml Met-BLG in absence of cell lines, the morphology and viability of virus particles were significantly affected as observed by electron microscopy, and the number of intact virus particles was reduced by roughly 65%.
Journal Article
Influenza virus A subtype H1N1 is inhibited by methylated beta-lactoglobulin
by
Billaudel, Sylviane
,
Haertlé, Thomas
,
Sitohy, Mahmoud
in
Avian flu
,
Carbon dioxide
,
Drug resistance
2010
Addition of methylated β-lactoglobulin (Met-BLG) in the medium of MDCK cell lines infected with influenza virus subtype H1N1 reduced hemagglutination activity (HA) in a concentration dependent manner. Antiviral activity of Met-BLG depended on its concentration, viral load, and duration of infection. Using 17 μg/ml of Met-BLG inhibited 50% of HA of H1N1 grown in MDCK cells at 1 MOI after 24 h incubation at 37°C and in 5% CO2. Extension of incubation time enhanced antiviral action since the same concentration of Met-BLG inhibited about 61% of viral activity after 48 h. This viral inhibition was accompanied by a protection of MDCK cells as observed by using neutral red or by direct microscope examination. Reduction of viral RNA replication upon the addition of Met-BLG (50 μg/ml) was observed by real time-PCR showing a reduction of viral log value of about 0·9. When viral stock solution was mixed with 25 μg/ml Met-BLG in absence of cell lines, the morphology and viability of virus particles were significantly affected as observed by electron microscopy, and the number of intact virus particles was reduced by roughly 65%. [PUBLICATION ABSTRACT]
Journal Article
Quantification of the aromatic potential of ripe fruit of Vanilla planifolia (Orchidaceae) and several of its closely and distantly related species and hybrids
2021
Vanilla flavor is derived from the cured fruits of two orchid species Vanilla planifolia and V. × tahitensis. About twenty other Vanilla species are also credited with scented fruits, but very little is known about their aromatic features. We investigated the aromatic compound content of the ripe fruits of 30 vanilla accessions obtained from eight species and three hybrids. Glucovanillin plus six phenolic and one anisic aglycones, extracted after enzymatic hydrolysis, were quantified by High-Performance Liquid Chromatography and Ultra-Violet detection. The analysis of the aromatic contents and the principal components showed clear-cut differences in the aromatic content of the species and varieties studied. The total content of aromatic compounds separated the three species most distantly related to V. planifolia, namely V. lindmaniana, V. crenulata and V. imperialis, from the other species notably by the absence of vanillin potential and a very low total aromatic potential (< 0.45% w/w dry matter). A clear gradient was observed between the different genotypes of V. planifolia, in particular for the total aromatic content (range 3.07–5.00% dry weight) and the vanillin potential (1.80–4.58%). Among all the analyzed samples, the greatest vanillin potential was observed in a V. planifolia x V. × tahitensis hybrid (7.46%). Anisyl alcohol was not detected in any of the 13 V. planifolia varieties but was detected in most of its close relatives such as V. sotoarenasii, V. bahiana, V. tahitensis, and V. pompona. Our data evidenced the very contrasting aromatic profiles of vanilla fruits, even among very close genotypes.
Journal Article
Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT)
2016
The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute.
This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582.
18 679 molecular analyses of 17 664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18–98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7–16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17 706 analyses for which data were available, HER2 mutations in 98 (1%) of 11 723, KRAS mutations in 4894 (29%) of 17 001, BRAF mutations in 262 (2%) of 13 906, and PIK3CA mutations in 252 (2%) of 10 678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8–25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7–38·2] for presence of a genetic alteration vs 33% [29·5–35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0–18·8] vs 9% [6·7–11·9]; p<0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2–10·7] vs 7·1 months [6·1–7·9]; p<0·0001) and overall survival (16·5 months [15·0–18·3] vs 11·8 months [10·1–13·5]; p<0·0001) compared with absence of a genetic alteration.
Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit.
French National Cancer Institute (INCa).
Journal Article
BepiColombo Science Investigations During Cruise and Flybys at the Earth, Venus and Mercury
by
Heyner, Daniel
,
Iwai, Kazumasa
,
Mangano, Valeria
in
Aerospace Technology and Astronautics
,
Astrophysics and Astroparticles
,
Bepi Colombo (ESA)
2021
The dual spacecraft mission BepiColombo is the first joint mission between the European Space Agency (ESA) and the Japanese Aerospace Exploration Agency (JAXA) to explore the planet Mercury. BepiColombo was launched from Kourou (French Guiana) on October 20th, 2018, in its packed configuration including two spacecraft, a transfer module, and a sunshield. BepiColombo cruise trajectory is a long journey into the inner heliosphere, and it includes one flyby of the Earth (in April 2020), two of Venus (in October 2020 and August 2021), and six of Mercury (starting from 2021), before orbit insertion in December 2025. A big part of the mission instruments will be fully operational during the mission cruise phase, allowing unprecedented investigation of the different environments that will encounter during the 7-years long cruise. The present paper reviews all the planetary flybys and some interesting cruise configurations. Additional scientific research that will emerge in the coming years is also discussed, including the instruments that can contribute.
Journal Article