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961.
A genetic linkage map of Theobroma cacao L. 总被引:2,自引:0,他引:2
C. Lanaud A. M. Risterucci A. K. J. N'Goran D. Clement M. H. Flament V. Laurent M. Falque 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1995,91(6-7):987-993
A linkage map of the cocoa genome comprising 193 loci has been constructed. These loci consist of 5 isozymes, 101 cDNA/RFLPs, 4 loci from genes of known function, 55 genomic DNA/RFLPs and 28 RAPDs. A population of 100 individuals derived from a cross between two heterozygous genotypes was used. Segregation analyses were performed with the JoinMap program. Ten linkage groups, which putatively correspond to the ten gametic chromosomes of cocoa, were identified. The map covers a total length of 759 cM with a 3.9 cM average distance between 2 markers. A small fraction (9%) of the markers deviated significantly from the expected Mendelian ratios. 相似文献
962.
Christine Delsarte Guillaume Etuin Laurent Petit 《Bioorganic & medicinal chemistry》2018,26(4):984-988
An improved process for the preparation of 1-methylcyclopropanol using the Kulinkovich reaction is described. The use of titanium tetramethoxide as catalyst resulted in minimal side product formation. The reaction, isolation and purification procedures were optimized so they can be easily implemented in multi-purpose equipment. 相似文献
963.
Arhamatoulaye Ma?ga Jon Merlin Elodie Marcon Céline Rouget Maud Larregola Bernard Gilquin Carole Fruchart-Gaillard Evelyne Lajeunesse Charles Marchetti Alain Lorphelin Laurent Bellanger Roger J. Summers Dana S. Hutchinson Bronwyn A. Evans Denis Servent Nicolas Gilles 《PloS one》2013,8(7)
ρ-Da1a is a three-finger fold toxin from green mamba venom that is highly selective for the α1A-adrenoceptor. This toxin has atypical pharmacological properties, including incomplete inhibition of 3H-prazosin or 125I-HEAT binding and insurmountable antagonist action. We aimed to clarify its mode of action at the α1A-adrenoceptor. The affinity (pKi 9.26) and selectivity of ρ-Da1a for the α1A-adrenoceptor were confirmed by comparing binding to human adrenoceptors expressed in eukaryotic cells. Equilibrium and kinetic binding experiments were used to demonstrate that ρ-Da1a, prazosin and HEAT compete at the α1A-adrenoceptor. ρ-Da1a did not affect the dissociation kinetics of 3H-prazosin or 125I-HEAT, and the IC50 of ρ-Da1a, determined by competition experiments, increased linearly with the concentration of radioligands used, while the residual binding by ρ-Da1a remained stable. The effect of ρ-Da1a on agonist-stimulated Ca2+ release was insurmountable in the presence of phenethylamine- or imidazoline-type agonists. Ten mutations in the orthosteric binding pocket of the α1A-adrenoceptor were evaluated for alterations in ρ-Da1a affinity. The D1063.32A and the S1885.42A/S1925.46A receptor mutations reduced toxin affinity moderately (6 and 7.6 times, respectively), while the F862.64A, F2886.51A and F3127.39A mutations diminished it dramatically by 18- to 93-fold. In addition, residue F862.64 was identified as a key interaction point for 125I-HEAT, as the variant F862.64A induced a 23-fold reduction in HEAT affinity. Unlike the M1 muscarinic acetylcholine receptor toxin MT7, ρ-Da1a interacts with the human α1A-adrenoceptor orthosteric pocket and shares receptor interaction points with antagonist (F862.64, F2886.51 and F3127.39) and agonist (F2886.51 and F3127.39) ligands. Its selectivity for the α1A-adrenoceptor may result, at least partly, from its interaction with the residue F862.64, which appears to be important also for HEAT binding. 相似文献
964.
Antoine Neuraz Laurent Chouchana Georgia Malamut Christine Le Beller Denis Roche Philippe Beaune Patrice Degoulet Anita Burgun Marie-Anne Loriot Paul Avillach 《PLoS computational biology》2013,9(12)
Phenome-Wide Association Studies (PheWAS) investigate whether genetic polymorphisms associated with a phenotype are also associated with other diagnoses. In this study, we have developed new methods to perform a PheWAS based on ICD-10 codes and biological test results, and to use a quantitative trait as the selection criterion. We tested our approach on thiopurine S-methyltransferase (TPMT) activity in patients treated by thiopurine drugs. We developed 2 aggregation methods for the ICD-10 codes: an ICD-10 hierarchy and a mapping to existing ICD-9-CM based PheWAS codes. Eleven biological test results were also analyzed using discretization algorithms. We applied these methods in patients having a TPMT activity assessment from the clinical data warehouse of a French academic hospital between January 2000 and July 2013. Data after initiation of thiopurine treatment were analyzed and patient groups were compared according to their TPMT activity level. A total of 442 patient records were analyzed representing 10,252 ICD-10 codes and 72,711 biological test results. The results from the ICD-9-CM based PheWAS codes and ICD-10 hierarchy codes were concordant. Cross-validation with the biological test results allowed us to validate the ICD phenotypes. Iron-deficiency anemia and diabetes mellitus were associated with a very high TPMT activity (p = 0.0004 and p = 0.0015, respectively). We describe here an original method to perform PheWAS on a quantitative trait using both ICD-10 diagnosis codes and biological test results to identify associated phenotypes. In the field of pharmacogenomics, PheWAS allow for the identification of new subgroups of patients who require personalized clinical and therapeutic management. 相似文献
965.
966.
Laurent Cattiaux Vanessa Porkolab Franck Fieschi Jean-Maurice Mallet 《Bioorganic & medicinal chemistry》2018,26(5):1006-1015
A branched amino acid was synthesized from methyl glucopyranoside; this amino acid presents three amino groups protected by Fmoc and one acid group and can be used in classic peptide synthesis. In parallel, similar azido terminated blocks were synthesized.Successive coupling reaction and deprotection afforded dendrimers with up to 27 azido functional groups. As an example of application, d-mannose and l-fucose residues were linked through CuAAC coupling and resulting glycodendrimers were evaluated in their interaction with DC-SIGN using SPR competition assay. 相似文献
967.
968.
969.
Mélanie Gaubert Marion Marlinge Marine Alessandrini Marc Laine Laurent Bonello Julien Fromonot Jennifer Cautela Franck Thuny Jeremie Barraud Giovanna Mottola Pascal Rossi Emmanuel Fenouillet Jean Ruf Régis Guieu Franck Paganelli 《Purinergic signalling》2018,14(2):191-199
The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI?<?1.67. We identified a linear correlation between SUA and RHI (R2 =?0.66 P <?0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients. 相似文献
970.
Jean-François Fournier Yushma Bhurruth-Alcor Branislav Musicki Jérome Aubert Michèle Aurelly Claire Bouix-Peter Karinne Bouquet Laurent Chantalat Marion Delorme Bénédicte Drean Gwenaelle Duvert Nicolas Fleury-Bregeot Blanche Gauthier Karine Grisendi Craig S. Harris Laurent F. Hennequin Tatiana Isabet Florence Joly Loïc Tomas 《Bioorganic & medicinal chemistry letters》2018,28(17):2985-2992
A series of squaramide-based hydroxamic acids were designed, synthesized and evaluated against human HDAC enzyme. Squaramides were found to be potent in the Hut78 cell line, but initially suffered from low solubility. Leads with improved solubility and metabolic profiles were shown to be class I, IIB and IV selective. 相似文献