Functional characterization of a melon alcohol acyl-transferase gene family involved in the biosynthesis of ester volatiles. Identification of the crucial role of a threonine residue for enzyme activity

Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT). We demonstrate here that, in Charentais melon (Cucumis melo var. cantalupensis), AAT are encoded by a gene family of at least four members with amino acid identity ranging from 84% (Cm-AAT1/Cm-AAT2) and 58% (Cm-AAT1/Cm-AAT3) to only 22% (Cm-AAT1/Cm-AAT4). All encoded proteins, except Cm-AAT2, were enzymatically active upon expression in yeast and show differential substrate preferences. Cm-AAT1 protein produces a wide range of short and long-chain acyl esters but has strong preference for the formation of E-2-hexenyl acetate and hexyl hexanoate. Cm-AAT3 also accepts a wide range of substrates but with very strong preference for producing benzyl acetate. Cm-AAT4 is almost exclusively devoted to the formation of acetates, with strong preference for cinnamoyl acetate. Site directed mutagenesis demonstrated that the failure of Cm-AAT2 to produce volatile esters is related to the presence of a 268-alanine residue instead of threonine as in all active AAT proteins. Mutating 268-A into 268-T of Cm-AAT2 restored enzyme activity, while mutating 268-T into 268-A abolished activity of Cm-AAT1. Activities of all three proteins measured with the prefered substrates sharply increase during fruit ripening. The expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. The data presented in this work suggest that the multiplicity of AAT genes accounts for the great diversity of esters formed in melon

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Study of the lineshape of the chi(c1) (3872) state

A study of the lineshape of the chi(c1) (3872) state is made using a data sample corresponding to an integrated luminosity of 3 fb(-1) collected in pp collisions at center-of-mass energies of 7 and 8 TeV with the LHCb detector. Candidate chi(c1)(3872) and psi(2S) mesons from b-hadron decays are selected in the J/psi pi(+)pi(-) decay mode. Describing the lineshape with a Breit-Wigner function, the mass splitting between the chi(c1 )(3872) and psi(2S) states, Delta m, and the width of the chi(c1 )(3872) state, Gamma(Bw), are determined to be (Delta m=185.598 +/- 0.067 +/- 0.068 Mev,)(Gamma BW=1.39 +/- 0.24 +/- 0.10 Mev,) where the first uncertainty is statistical and the second systematic. Using a Flatte-inspired model, the mode and full width at half maximum of the lineshape are determined to be (mode=3871.69+0.00+0.05 MeV.)(FWHM=0.22-0.04+0.13+0.07+0.11-0.06-0.13 MeV, ) An investigation of the analytic structure of the Flatte amplitude reveals a pole structure, which is compatible with a quasibound D-0(D) over bar*(0) state but a quasivirtual state is still allowed at the level of 2 standard deviations

Measurement of the CKM angle γγ in B±→DK±B^\pm\to D K^\pm and B±→Dπ±B^\pm \to D π^\pm decays with D→KS0h+h−D \to K_\mathrm S^0 h^+ h^-

A measurement of $CP$-violating observables is performed using the decays $B^\pm\to D K^\pm$ and $B^\pm\to D \pi^\pm$, where the $D$ meson is reconstructed in one of the self-conjugate three-body final states $K_{\mathrm S}\pi^+\pi^-$ and $K_{\mathrm S}K^+K^-$ (commonly denoted $K_{\mathrm S} h^+h^-$). The decays are analysed in bins of the $D$-decay phase space, leading to a measurement that is independent of the modelling of the $D$-decay amplitude. The observables are interpreted in terms of the CKM angle $\gamma$. Using a data sample corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$ collected in proton-proton collisions at centre-of-mass energies of $7$, $8$, and $13\,\text{TeV}$ with the LHCb experiment, $\gamma$ is measured to be $\left(68.7^{+5.2}_{-5.1}\right)^\circ$. The hadronic parameters $r_B^{DK}$, $r_B^{D\pi}$, $\delta_B^{DK}$, and $\delta_B^{D\pi}$, which are the ratios and strong-phase differences of the suppressed and favoured $B^\pm$ decays, are also reported

Study of the doubly charmed tetraquark T+cc

Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar T+cc tetraquark with a quark content of ccu⎯⎯⎯d⎯⎯⎯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector T+cc state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the T+cc state. In addition, an unexpected dependence of the production rate on track multiplicity is observed