Resonances from meson-meson scattering in U(3) CHPT

In this work, the complete one loop calculation of meson-meson scattering amplitudes within U(3)\otimes U(3) chiral perturbation theory with explicit resonance states is carried out for the first time. Partial waves are unitarized from the perturbative calculation employing a non-perturbative approach based on the N/D method. Once experimental data are reproduced in a satisfactory way we then study the resonance properties, such as the pole positions, corresponding residues and their N_C behaviors. The resulting N_C dependence is the first one in the literature that takes into account the fact that the \eta_1 becomes the ninth Goldstone boson in the chiral limit for large N_C. Within this scheme the vector resonances studied, \rho(770), K^*(892) and \phi(1020), follow an N_C trajectory in agreement with their standard \bar{q}q interpretation. The scalars f_0(1370), a_0(1450) and K^*(1430) also have for large N_C a \bar{q}q pole position trajectory and all of them tend to a bare octet of scalar resonances around 1.4 GeV. The f_0(980) tends asymptotically to the bare pole position of a singlet scalar resonance around 1 GeV. The \sigma, \kappa and a_0(980) scalar resonances have a very different N_C behavior. The case of the \sigma resonance is analyzed with special detail.Comment: 50 pages, 15 figures, 1 table. Enlarged version with more detail comparisons with previous results in the literature. To match with accepted version for publicatio

Tree amplitudes of noncommutative U(N) Yang-Mills Theory

Following the spirit of S-matrix program, we proposed a modified Britto-Cachazo-Feng-Witten recursion relation for tree amplitudes of noncommutative U(N) Yang-Mills theory. Starting from three-point amplitudes, one can use this modified BCFW recursion relation to compute or analyze color-ordered tree amplitudes without relying on any detail information of noncommutative Yang-Mills theory. After clarifying the color structure of noncommutative tree amplitudes, we wrote down the noncommutative analogies of U(1)-decoupling, Kleiss-Kuijf and Bern-Carrasco-Johansson relations for color-ordered tree amplitudes, and proved them using the modified BCFW recursion relation.Comment: 24 pages, 3 figures. v2 References added. v3 some typos correcte

Inhibition of Hypoxia-Inducible Factor-1α (HIF-1α) Protein Synthesis by DNA damage inducing agents

10.1371/journal.pone.0010522PLoS ONE55

Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes

Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function. We performed whole-exome sequencing (WES) in 84 (78 unrelated) unsolved PME-affected individuals, with or without additional family members, to discover novel causes. We identified likely disease-causing variants in 24 out of 78 (31%) unrelated individuals, despite previous genetic analyses. The diagnostic yield was significantly higher for individuals studied as trios or families (14/28) versus singletons (10/50) (OR = 3.9, p value = 0.01, Fisher's exact test). The 24 likely solved cases of PME involved 18 genes. First, we found and functionally validated five heterozygous variants in NUS1 and DHDDS and a homozygous variant in ALG10, with no previous disease associations. All three genes are involved in dolichol-dependent protein glycosylation, a pathway not previously implicated in PME. Second, we independently validate SEMA6B as a dominant PME gene in two unrelated individuals. Third, in five families, we identified variants in established PME genes; three with intronic or copy-number changes (CLN6, GBA, NEU1) and two very rare causes (ASAH1, CERS1). Fourth, we found a group of genes usually associated with developmental and epileptic encephalopathies, but here, remarkably, presenting as PME, with or without prior developmental delay. Our systematic analysis of these cases suggests that the small residuum of unsolved cases will most likely be a collection of very rare, genetically heterogeneous etiologies.Peer reviewe

Evaluation of methods and marker systems in genomic selection of oil palm (Elaeis guineensis Jacq.)

Background Genomic selection (GS) uses genome-wide markers as an attempt to accelerate genetic gain in breeding programs of both animals and plants. This approach is particularly useful for perennial crops such as oil palm, which have long breeding cycles, and for which the optimal method for GS is still under debate. In this study, we evaluated the effect of different marker systems and modeling methods for implementing GS in an introgressed dura family derived from a Deli dura x Nigerian dura (Deli x Nigerian) with 112 individuals. This family is an important breeding source for developing new mother palms for superior oil yield and bunch characters. The traits of interest selected for this study were fruit-to-bunch (F/B), shell-to-fruit (S/F), kernel-to-fruit (K/F), mesocarp-to-fruit (M/F), oil per palm (O/P) and oil-to-dry mesocarp (O/DM). The marker systems evaluated were simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs). RR-BLUP, Bayesian A, B, Cπ, LASSO, Ridge Regression and two machine learning methods (SVM and Random Forest) were used to evaluate GS accuracy of the traits. Results The kinship coefficient between individuals in this family ranged from 0.35 to 0.62. S/F and O/DM had the highest genomic heritability, whereas F/B and O/P had the lowest. The accuracies using 135 SSRs were low, with accuracies of the traits around 0.20. The average accuracy of machine learning methods was 0.24, as compared to 0.20 achieved by other methods. The trait with the highest mean accuracy was F/B (0.28), while the lowest were both M/F and O/P (0.18). By using whole genomic SNPs, the accuracies for all traits, especially for O/DM (0.43), S/F (0.39) and M/F (0.30) were improved. The average accuracy of machine learning methods was 0.32, compared to 0.31 achieved by other methods. Conclusion Due to high genomic resolution, the use of whole-genome SNPs improved the efficiency of GS dramatically for oil palm and is recommended for dura breeding programs. Machine learning slightly outperformed other methods, but required parameters optimization for GS implementation

Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus

Peer reviewe

Sex-Related Differences in Medically Treated Moderate Aortic Stenosis

BackgroundRecent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS.MethodsIn this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement.ResultsA total of 1895 patients with moderate AS (age 73 ± 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3- and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) (p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes.ConclusionsLV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed.</p

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk