Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable

Inclusive and multiplicity dependent production of electrons from heavy-flavour hadron decays in pp and p-Pb collisions

Measurements of the production of electrons from heavy-flavour hadron decays in pp collisions at root s = 13 TeV at midrapidity with the ALICE detector are presented down to a transverse momentum (p(T)) of 0.2 GeV/c and up to p(T) = 35 GeV/c, which is the largest momentum range probed for inclusive electron measurements in ALICE. In p-Pb collisions, the production cross section and the nuclear modification factor of electrons from heavy-flavour hadron decays are measured in the p(T) range 0.5 < p(T) < 26 GeV/c at root s(NN) = 8.16 TeV. The nuclear modification factor is found to be consistent with unity within the statistical and systematic uncertainties. In both collision systems, first measurements of the yields of electrons from heavy-flavour hadron decays in different multiplicity intervals normalised to the multiplicity-integrated yield (self-normalised yield) at midrapidity are reported as a function of the self-normalised charged-particle multiplicity estimated at midrapidity. The self-normalised yields in pp and p-Pb collisions grow faster than linear with the self-normalised multiplicity. A strong p(T) dependence is observed in pp collisions, where the yield of high-p(T) electrons increases faster as a function of multiplicity than the one of low-p(T) electrons. The measurement in p-Pb collisions shows no p(T) dependence within uncertainties. The self-normalised yields in pp and p-Pb collisions are compared with measurements of other heavy-flavour, light-flavour, and strange particles, and with Monte Carlo simulations

Accessing the strong interaction between Λ baryons and charged kaons with the femtoscopy technique at the LHC

The interaction between Λ baryons and kaons/antikaons is a crucial ingredient for the strangeness S=0 and S=-2 sector of the meson–baryon interaction at low energies. In particular, the Lambda-Kbar might help in understanding the origin of states such as the Csi(1620), whose nature and properties are still under debate. Experimental data on Lambda-K and Lambda-Kbar systems are scarce, leading to large uncertainties and tension between the available theoretical predictions constrained by such data. In this Letter we present the measurements of Λ–KK− and Λ–KK+ correlations obtained in the high-multiplicity triggered data sample in pp collisions at sqrt(s) = 13 TeV recorded by ALICE at the LHC. The correlation function for both pairs is modeled using the Lednický–Lyuboshits analytical formula and the corresponding scattering parameters are extracted. The Λ–KK+ correlations show the presence of several structures at relative momenta k* above 200 MeV/c, compatible with the Ω baryon, the , and resonances decaying into Λ–K− pairs. The low k* region in the Λ–KK+ also exhibits the presence of the state, expected to strongly couple to the measured pair. The presented data allow to access the ΛK+ and ΛK− strong interaction with an unprecedented precision and deliver the first experimental observation of the decaying into ΛK−

Measurement of the non-prompt D-meson fraction as a function of multiplicity in proton-proton collisions at s \sqrt{s} = 13 TeV

The fractions of non-prompt (i.e. originating from beauty-hadron decays) D0 and D+ mesons with respect to the inclusive yield are measured as a function of the charged-particle multiplicity in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV with the ALICE detector at the LHC. The results are reported in intervals of transverse momentum (pT) and integrated in the range 1 < pT < 24 GeV/c. The fraction of non-prompt D0 and D+ mesons is found to increase slightly as a function of pT in all the measured multiplicity intervals, while no significant dependence on the charged- particle multiplicity is observed. In order to investigate the production and hadronisation mechanisms of charm and beauty quarks, the results are compared to PYTHIA 8 as well as EPOS 3 and EPOS 4 Monte Carlo simulations, and to calculations based on the colour glass condensate including three-pomeron fusion

Light (anti)nuclei production in Pb-Pb collisions at sNN=5.02 TeV

The measurement of the production of deuterons, tritons and 3 He and their antiparticles in Pb-Pb collisions at √s NN = 5.02 TeV is presented in this article. The measurements are carried out at midrapidity (|y| < 0.5) as a function of collision centrality using the ALICE detector. The pT -integrated yields, the coalescence parameters and the ratios to protons and antiprotons are reported and compared with nucleosynthesis models. The comparison of these results in different collision systems at different center-of-mass collision energies reveals a suppression of nucleus production in small systems. In the Statistical Hadronisation Model framework, this can be explained by a small correlation volume where the baryon number is conserved, as already shown in previous fluctuation analyses. However, a different size of the correlation volume is required to describe the proton yields in the same data sets. The coalescence model can describe this suppression by the fact that the wave functions of the nuclei are large and the fireball size starts to become comparable and even much smaller than the actual nucleus at low multiplicities

Production of pions, kaons, and protons as a function of the relative transverse activity classifier in pp collisions at s \sqrt{s} = 13 TeV

Abstract: The production of π±, K±, and ( p )p is measured in pp collisions at √s = 13 TeV in different topological regions of the events. Particle transverse momentum (pT) spectra are measured in the “toward”, “transverse”, and “away” angular regions defined with respect to the direction of the leading particle in the event. While the toward and away regions contain the fragmentation products of the near-side and away-side jets, respectively, the transverse region is dominated by particles from the Underlying Event (UE). The relative transverse activity classifier, RT = NT/〈NT〉, is used to group events according to their UE activity, where NT is the measured charged-particle multiplicity per event in the transverse region and 〈NT〉 is the mean value over all the analysed events. The first measurements of identified particle pT spectra as a function of RT in the three topological regions are reported. It is found that the yield of high transverse momentum particles relative to the RT-integrated measurement decreases with increasing RT in both the toward and the away regions, indicating that the softer UE dominates particle production as RT increases and validating that RT can be used to control the magnitude of the UE. Conversely, the spectral shapes in the transverse region harden significantly with increasing RT. This hardening follows a mass ordering, being more significant for heavier particles. Finally, it is observed that the pT-differential particle ratios (p + p )/(π+ + π−) and (K+ + K−)/(π+ + π−) in the low UE limit (RT → 0) approach expectations from Monte Carlo generators such as PYTHIA 8 with Monash 2013 tune and EPOS LHC, where the jet-fragmentation models have been tuned to reproduce e+e− results

First measurement of Λc+ production down to pT=0 in pp and p-Pb collisions at sNN=5.02 TeV

The production of prompt Lambda+c baryons has been measured at midrapidity in the transverse momentum interval 0 < pT < 1 GeV/c for the first time, in pp and p–Pb collisions at a center-of-mass energy per nucleon-nucleon collision √s NN = 5.02 TeV. The measurement was performed in the decay channel Lambda+c → pK0S by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The pT -integrated Lambda+c production cross sections in both collision systems were determined and used along with the measured yields in Pb–Pb collisions to compute the pT -integrated nuclear modification factors R pPb and R AA of Lambda+c baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The Lambda+c /D0 baryon-to-meson yield ratio is reported for pp and p–Pb collisions. Comparisons with models that include modified hadronization processes are presented, and the implications of the results on the understanding of charm hadronization in hadronic collisions are discussed. A significant (3.7σ ) modification of the mean transverse momentum of Lambda+c baryons is seen in p–Pb collisions with respect to pp collisions, while the pT -integrated Lambda+c /D0 yield ratio was found to be consistent between the two collision systems within the uncertainties

Investigation of K+K- interactions via femtoscopy in Pb-Pb collisions at sNN =2.76 TeV at the CERN Large Hadron Collider

Femtoscopic correlations of nonidentical charged kaons (K+K-) are studied in Pb-Pb collisions at a center-of-mass energy per nucleon-nucleon collision sNN=2.76 TeV by ALICE at the CERN Large Hadron Collider. One-dimensional K+K- correlation functions are analyzed in three centrality classes and eight intervals of particle-pair transverse momentum. The Lednický and Luboshitz interaction model used in the K+K- analysis includes the final-state Coulomb interactions between kaons and the final-state interaction through a0(980) and f0(980) resonances. The mass of f0(980) and coupling were extracted from the fit to K+K- correlation functions using the femtoscopic technique. The measured mass and width of the f0(980) resonance are consistent with other published measurements. The height of the φ(1020) meson peak present in the K+K- correlation function rapidly decreases with increasing source radius, qualitatively in agreement with an inverse volume dependence. A phenomenological fit to this trend suggests that the φ(1020) meson yield is dominated by particles produced directly from the hadronization of the system. The small fraction subsequently produced by final-state interactions could not be precisely quantified with data presented in this paper and will be assessed in future work

Measurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H

The most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process). The measured values τ=[253±11(stat)±6(syst)]  ps and B_{Λ}=[102±63(stat)±67(syst)]  keV are compatible with predictions from effective field theories and confirm that the _{Λ}^{3}H structure is consistent with a weakly bound system