0400: Degenerative calcific mitral stenosis in patients referred for high surgical risk aortic stenosis: detection and quantification by multi-detector computed tomography

BackgroundMitral annular calcifications (MAC) is a common finding in elder patients referred for transcatheter aortic valve implantation (TAVI), sometimes responsible of significant degenerative calcified mitral stenosis (CaMS), but prevalence of both is poorly defined. Multidectector computed tomography (MDCT) allows fine quantification of calcifications and is a reliable tool in rheumatic mitral stenosis, but its contribution in CaMS remains unknown. Our objective was to estimate prevalence of MAC and CaMS in patients referred for TAVI using MDCT, and determine morphological factors leading from MAC to CaMS.Methods and resultsA cohort of 346 consecutive patients referred for TAVI evaluation was screened by MDCT for MAC. One hundred and seventy four patients were positive for MAC. Among these patients, 165 patients had mitral valve area (MVA) assessable by MDCT planimetry (mean age 84 years). Analysis by segment revealed calcifications on: A1 30.9%, A2 29.1%, A3 42.4%, P1 56.4%, P2 78.8%, P3 69.7%. Mean mitral calcification volume and MVA were 1020±1398mm3 and 246±90mm 2, respectively. CaMS were severe, moderate and mild in 2.4%, 21.8% and 9.7% patients, respectively. Correlation between mitral calcification volume and MVA was significant but moderate (r=–0.433). On multivariate analysis, MVA was independently linked to mitral calcification volume, aortic annular area and specific patterns of mitral leaflet calcification underlining the role of A2 (AUC 0.81). Interobserver reproducibility of MVA was high (ICC 0.935).ConclusionsMDCT allows detailed assessment of MAC in TAVI populations, demonstrating high prevalence, and quantification of CaMS with high reproducibility. Mitral analysis should become routine during MDCT screening before TAVI as it may significantly alter the therapeutic strategy

Complex population structure and haplotype patterns in the Western European honey bee from sequencing a large panel of haploid drones:Sequencing haploid honey bee drones

International audienceHoney bee subspecies originate from specific geographical areas in Africa, Europe and the Middle East, and beekeepers interested in specific phenotypes have imported genetic material to regions outside of the bees' original range for use either in pure lines or controlled crosses. Moreover, imported drones are present in the environment and mate naturally with queens from the local subspecies. The resulting admixture complicates population genetics analyses, and population stratification can be a major problem for association studies. To better understand Western European honey bee populations, we produced a whole genome sequence and single nucleotide polymorphism (SNP) genotype data set from 870 haploid drones and demonstrate its utility for the identification of nine genetic backgrounds and various degrees of admixture in a subset of 629 samples. Five backgrounds identified correspond to subspecies, two to isolated populations on islands and two to managed populations. We also highlight several large haplotype blocks, some of which coincide with the position of centromeres. The largest is 3.6 Mb long and represents 21% of chromosome 11, with two major haplotypes corresponding to the two dominant genetic backgrounds identified. This large naturally phased data set is available as a single vcf file that can now serve as a reference for subsequent populations genomics studies in the honey bee, such as (i) selecting individuals of verified homogeneous genetic backgrounds as references, (ii) imputing genotypes from a lower-density data set generated by an SNP-chip or by low-pass sequencing, or (iii) selecting SNPs compatible with the requirements of genotyping chips

Complex population structure and haplotype patterns in the Western European honey bee from sequencing a large panel of haploid drones

Honey bee subspecies originate from specific geographical areas in Africa, Europe and the Middle East, and beekeepers interested in specific phenotypes have imported genetic material to regions outside of the bees' original range for use either in pure lines or controlled crosses. Moreover, imported drones are present in the environment and mate naturally with queens from the local subspecies. The resulting admixture complicates population genetics analyses, and population stratification can be a major problem for association studies. To better understand Western European honey bee populations, we produced a whole genome sequence and single nucleotide polymorphism (SNP) genotype data set from 870 haploid drones and demonstrate its utility for the identification of nine genetic backgrounds and various degrees of admixture in a subset of 629 samples. Five backgrounds identified correspond to subspecies, two to isolated populations on islands and two to managed populations. We also highlight several large haplotype blocks, some of which coincide with the position of centromeres. The largest is 3.6 Mb long and represents 21% of chromosome 11, with two major haplotypes corresponding to the two dominant genetic backgrounds identified. This large naturally phased data set is available as a single vcf file that can now serve as a reference for subsequent populations genomics studies in the honey bee, such as (i) selecting individuals of verified homogeneous genetic backgrounds as references, (ii) imputing genotypes from a lower-density data set generated by an SNP-chip or by low-pass sequencing, or (iii) selecting SNPs compatible with the requirements of genotyping chips.This work was performed in collaboration with the GeT platform, Toulouse (France), a partner of the National Infrastructure France Génomique, thanks to support by the Commissariat aux Grands Invetissements (ANR-10-INBS-0009). Bioinformatics analyses were performed on the GenoToul Bioinfo computer cluster. This work was funded by a grant from the INRA Département de Génétique Animale (INRA Animal Genetics division) and by the SeqApiPop programme, funded by the FranceAgriMer grant 14-21-AT. We thank John Kefuss for helpful discussions. We thank Andrew Abrahams for providing honey bee samples from Colonsay (Scotland), the Association Conservatoire de l'Abeille Noire Bretonne (ACANB) for samples from Ouessant (France), CETA de Savoie for sample from Savoie, ADAPI for samples from Porquerolles and all beekeepers and bee breeders who kindly participated in this study by providing samples from their colonies.info:eu-repo/semantics/publishedVersio

Autosomal and mitochondrial adaptation following admixture: a case study on the honeybees of Reunion Island.

The honeybee population of the tropical Reunion Island is a genetic admixture of the Apis mellifera unicolor subspecies, originally described in Madagascar, and of European subspecies, mainly A.m. carnica and A. m. ligustica, regularly imported to the island since the late 19th century. We took advantage of this population to study genetic admixing of the tropical-adapted indigenous and temperate-adapted European genetic backgrounds. Whole genome sequencing of 30 workers and 6 males from Reunion, compared to samples from Europe, Madagascar, Mauritius, Rodrigues and the Seychelles, revealed the Reunion honeybee population to be composed on average of 53.2 ± 5.9% A. m. unicolor nuclear genomic background, the rest being mainly composed of A. m. carnica and to a lesser extent A. m. ligustica. In striking contrast to this, only one out of the 36 honeybees from Reunion had a mitochondrial genome of European origin, suggesting selection has favoured the A. m. unicolor mitotype, which is possibly better adapted to the island's bioclimate. Local ancestry was determined along the chromosomes for all Reunion samples, and a test for preferential selection for the A. m. unicolor or European background revealed 15 regions significantly associated with the A. m. unicolor lineage and 9 regions with the European lineage. Our results provide insights into the long-term consequences of introducing exotic specimen on the nuclear and mitochondrial genomes of locally-adapted populations. (Résumé d'auteur

RRKM modeling of collision activated reaction/collision induced dissociation experiments: Energy profile determination for phenylethyne incorporation on palladium (II)?phosphinous acid complex

International audienceWe have recently reported a detailed ESI-collision activated reaction/collision activated reaction (ESI-CAR/CAR) and ESI-collision activated reaction/collision induced dissociation (ESI-CAR/CID) mass spectrometric investigation, combined with quantum chemistry calculations, to elucidate the reaction mechanism of [2 + 1] cycloaddition between alkyne and norbornadiene using a Pd(II) complex as catalyst. The coordination mode of alkyne on the metal was shown to be an essential preliminary step of the reaction, but mass spectrometric results were difficult to rationalize according to changes in the experimental conditions. In this work we present a detailed RRKM modeling of these experiments using MassKinetics software. We demonstrate how essential kinetic modeling is in order to interpret these experiments: both for phenomenological aspects (understand spectra and changes in their pattern due to energetic modifications) and as a link between quantum chemistry results and tandem MS experiments. Complete energy profile for isomerization and decomposition processes of [Pd[(t-Bu)(Ph)PO]2H + PhCCH]+ complexes has been determined through kinetic modeling of experimental data.Detailed modeling procedure is presented; approximations discussed and validated for quantitative comparison with quantum chemistry calculations. Agreement between isomerization barriers determined with kinetic modeling of experimental data and those determined through quantum chemistry was found to be within few kcal/mol supporting the validity of the approach and assumptions made in the model

Impact of resonant excitation parameters on the intra-complex gas phase HDX within small non-covalent systems

International audienceObjectiveExploring unexpected H/D exchanges between the partners of small sodiated noncovalent complex (NCC) anions constituted by fructose 6-phosphate (F6P) and arginine (R) for distinguishing between their solvated salt (SS) and hydrogen bonded (HB) forms.Main observationsComplementary enrichment(+D)/depletion(-D) detected in diagnostic product ions related to each partner favored under resonant excitation conditions by increasing excitation parameter values (ExcTime, ExcQ and NCE). Suggested stepwise process involving hydride/deuteride transfer from specific carbon atom to another (e.g. nitrogen) atom within SS form of NCC rather than proton/deuteron exchanges

Impact of resonant excitation parameters on the intra-complex gas phase HDX within small non-covalent systems

International audienceObjectiveExploring unexpected H/D exchanges between the partners of small sodiated noncovalent complex (NCC) anions constituted by fructose 6-phosphate (F6P) and arginine (R) for distinguishing between their solvated salt (SS) and hydrogen bonded (HB) forms.Main observationsComplementary enrichment(+D)/depletion(-D) detected in diagnostic product ions related to each partner favored under resonant excitation conditions by increasing excitation parameter values (ExcTime, ExcQ and NCE). Suggested stepwise process involving hydride/deuteride transfer from specific carbon atom to another (e.g. nitrogen) atom within SS form of NCC rather than proton/deuteron exchanges

Extended kinetic method and RRKM modeling to reinvestigate proline’s proton affinity and approach the meaning of effective temperature

International audienc

Impact of resonant excitation parameters on the intra-complex gas phase HDX within small non-covalent systems

International audienceObjectiveExploring unexpected H/D exchanges between the partners of small sodiated noncovalent complex (NCC) anions constituted by fructose 6-phosphate (F6P) and arginine (R) for distinguishing between their solvated salt (SS) and hydrogen bonded (HB) forms.Main observationsComplementary enrichment(+D)/depletion(-D) detected in diagnostic product ions related to each partner favored under resonant excitation conditions by increasing excitation parameter values (ExcTime, ExcQ and NCE). Suggested stepwise process involving hydride/deuteride transfer from specific carbon atom to another (e.g. nitrogen) atom within SS form of NCC rather than proton/deuteron exchanges