MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro

BACKGROUND: MicroRNAs (miRNAs) are small regulatory molecules that cause translational repression by base pairing with target mRNAs. Cumulative evidence suggests that changes in miRNA expression may in part underlie the pathophysiology and treatment of neuropsychiatric disorders, including major depressive disorder (MDD). METHODS: A miRNA expression assay that can simultaneously detect 423 rat miRNAs (miRBase v.17) was used to profile the prefrontal cortex (PFC) of a genetic rat model of MDD (the Flinders Sensitive Line [FSL]) and the controls, the Flinders Resistant Line (FRL). Gene expression data from the PFC of FSL/FRL animals (GEO accession no. GSE20388) were used to guide mRNA target selection. Luciferase reporter assays were used to verify miRNA targets in vitro. RESULTS: We identified 23 miRNAs that were downregulated in the PFC of the FSL model compared with controls. Interestingly, one of the identified miRNAs (miR-101b) is highly conserved between rat and human and was recently found to be downregulated in the PFC of depressed suicide subjects. Using a combination of in silico and in vitro analyses, we found that miR-101b targets the neuronal glutamate transporter SLC1A1 (also known as EAAC1 or EAAT3). Accordingly, both mRNA and protein levels of SLC1A1 were found to be upregulated in the PFC of the FSL model. CONCLUSIONS: Besides providing a list of novel miRNAs associated with depression-like states, this preclinical study replicated the human association of miR-101 with depression. In addition, since one of the targets of miR-101b appears to be a glutamate transporter, our preclinical data support the hypothesis of a glutamatergic dysregulation being implicated in the etiology of depression

Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A

The aim of the present study was to identify the molecular mechanism behind ventricular tachycardia in a patient with Brugada syndrome. Arrhythmias in patients with Brugada syndrome often occur during sleep. However, a 28-year-old man with no previously documented arrhythmia or syncope who experienced shortness of breath and chest pain during agitation is described. An electrocardiogram revealed monomorphic ventricular tachycardia; after he was converted to nodal rhythm, he spontaneously went into sinus rhythm, and showed classic Brugada changes with coved ST elevation in leads V(1) to V(2). Mutation analysis of SCN5A revealed a novel mutation, 3480 deletion T frame shift mutation, resulting in premature truncation of the protein. Heterologous expression of this truncated protein in human embryonic kidney 293 cells showed a markedly reduced protein expression level. By performing whole-cell patch clamp experiments using human embryonic kidney 293 cells transfected with the mutated SCN5A, no current could be recorded. Hence, the results suggest that the patient suffered from haploinsufficiency of Na(v)1.5, and that this mutation was the cause of his Brugada syndrome

Measurements of the groomed and ungroomed jet angularities in pp collisions at s \sqrt{s} = 5.02 TeV

International audienceThe jet angularities are a class of jet substructure observables which characterize the angular and momentum distribution of particles within jets. These observables are sensitive to momentum scales ranging from perturbative hard scatterings to nonperturbative fragmentation into final-state hadrons. We report measurements of several groomed and ungroomed jet angularities in pp collisions at $\sqrt{s}$ = 5.02 TeV with the ALICE detector. Jets are reconstructed using charged particle tracks at midrapidity (|η| < 0.9). The anti-k$_{T}$ algorithm is used with jet resolution parameters R = 0.2 and R = 0.4 for several transverse momentum {p}_{\mathrm{T}}^{\mathrm{ch}} ^{jet} intervals in the 20–100 GeV/c range. Using the jet grooming algorithm Soft Drop, the sensitivity to softer, wide-angle processes, as well as the underlying event, can be reduced in a way which is well-controlled in theoretical calculations. We report the ungroomed jet angularities, λ$_{α}$, and groomed jet angularities, λ$_{α,g}$, to investigate the interplay between perturbative and nonperturbative effects at low jet momenta. Various angular exponent parameters α = 1, 1.5, 2, and 3 are used to systematically vary the sensitivity of the observable to collinear and soft radiation. Results are compared to analytical predictions at next-to-leading-logarithmic accuracy, which provide a generally good description of the data in the perturbative regime but exhibit discrepancies in the nonperturbative regime. Moreover, these measurements serve as a baseline for future ones in heavy-ion collisions by providing new insight into the interplay between perturbative and nonperturbative effects in the angular and momentum substructure of jets. They supply crucial guidance on the selection of jet resolution parameter, jet transverse momentum, and angular scaling variable for jet quenching studies.[graphic not available: see fulltext

Inclusive quarkonium production in pp collisions at s=5.02\sqrt{s} = 5.02 TeV

This article reports on the inclusive production cross section of several quarkonium states, $\mathrm{J}/\psi$, $\psi {\rm (2S)}$, $\Upsilon\rm(1S)$, $\Upsilon\rm(2S)$, and $\Upsilon\rm(3S)$, measured with the ALICE detector at the LHC, in \pp collisions at $\sqrt{s} = 5.02$ TeV. The analysis is performed in the dimuon decay channel at forward rapidity ($2.5 < y < 4$). The measured cross sections, assuming unpolarized quarkonia, are: $\sigma_{\mathrm{J}/\psi} = 5.88 \pm 0.03 \pm 0.34\ \mu$b, $\sigma_{\psi {\rm (2S)}} = 0.87 \pm 0.06 \pm 0.10\ \mu$b, $\sigma_{\Upsilon\rm(1S)} = 45.5 \pm 3.9 \pm 3.5$ nb, $\sigma_{\Upsilon\rm(2S)} = 22.4 \pm 3.2 \pm 2.7$ nb, and $\sigma_{\Upsilon\rm(3S)} = 4.9 \pm 2.2 \pm 1.0$ nb, where the first (second) uncertainty is the statistical (systematic) one. The transverse-momentum ($p_{\rm T}$) and rapidity ($y$) differential cross sections for $\mathrm{J}/\psi$, $\psi {\rm (2S)}$, $\Upsilon\rm(1S)$, and the $\psi {\rm (2S)}$-to-$\mathrm{J}/\psi$ cross section ratios are presented. For the first time, the cross sections of the three $\Upsilon$ states, as well as the $\psi {\rm (2S)}$ one as a function of $p_{\rm T}$ and $y$, are measured at $\sqrt{s} = 5.02$ TeV at forward rapidity. These measurements also significantly extend the $\mathrm{J}/\psi$$p_{\rm T}$ reach with respect to previously published results. A comparison with ALICE measurements in pp collisions at $\sqrt{s} = 2.76$, 7, 8, and 13 TeV is presented and the energy dependence of quarkonium production cross sections is discussed. Finally, the results are compared with the predictions from several production models

Forward rapidity J/ψ production as a function of charged-particle multiplicity in pp collisions at s \sqrt{s} = 5.02 and 13 TeV

International audienceThe production of J/ψ is measured as a function of charged-particle multiplicity at forward rapidity in proton-proton (pp) collisions at center-of-mass energies $\sqrt{s}$ = 5.02 and 13 TeV. The J/ψ mesons are reconstructed via their decay into dimuons in the rapidity interval (2.5 < y < 4.0), whereas the charged-particle multiplicity density (dN$_{ch}$/dη) is measured at midrapidity (|η| < 1). The production rate as a function of multiplicity is reported as the ratio of the yield in a given multiplicity interval to the multiplicity-integrated one. This observable shows a linear increase with charged-particle multiplicity normalized to the corresponding average value for inelastic events (dN$_{ch}$/dη/〈dN$_{ch}$/dη〉), at both the colliding energies. Measurements are compared with available ALICE results at midrapidity and theoretical model calculations. First measurement of the mean transverse momentum (〈p$_{T}$〉) of J/ψ in pp collisions exhibits an increasing trend as a function of dN$_{ch}$/dη/〈dN$_{ch}$/dη〉 showing a saturation towards high charged-particle multiplicities.[graphic not available: see fulltext

Underlying-event properties in pp and p–Pb collisions at √sNN = 5.02 TeV

We report about the properties of the underlying event measured with ALICE at the LHC in pp and p−Pb collisions at sNN−−−√=5.02 TeV. The event activity, quantified by charged-particle number and summed-pT densities, is measured as a function of the leading-particle transverse momentum (ptrigT). These quantities are studied in three azimuthal-angle regions relative to the leading particle in the event: toward, away, and transverse. Results are presented for three different pT thresholds (0.15, 0.5, and 1 GeV/c) at mid-pseudorapidity (|η|10 GeV/c, whereas for lower ptrigT values the event activity is slightly higher in p−Pb than in pp collisions. The measurements are compared with predictions from the PYTHIA 8 and EPOS LHC Monte Carlo event generators

Measurement of the Cross Sections of Ξc0\Xi^0_{c} and Ξc+\Xi^+_{c} Baryons and of the Branching-Fraction Ratio BR(Ξc0→Ξ−e+νe\Xi^0_{c} \rightarrow \Xi^-{e}^+\nu_{ e})/BR(Ξc0→Ξ−π+\Xi^0_{c} \rightarrow \Xi^-\pi^+) in pp collisions at 13 TeV

The $p_T$-differential cross sections of prompt charm-strange baryons Ξ$_c^0$ and Ξ$_c^+$ were measured at midrapidity (|y|<0.5) in proton-proton (pp) collisions at a center-of-mass energy $\sqrt{s}$ = 13 TeV with the ALICE detector at the LHC. The Ξ$_c^0$ baryon was reconstructed via both the semileptonic decay (Ξ$^-$e$^+$ν$_e$) and the hadronic decay (Ξ$^-$π$^+$) channels. The Ξ$_c^+$ baryon was reconstructed via the hadronic decay (Ξ$^-$π$^+$π$^+$) channel. The branching-fraction ratio BR(Ξ$_c^0$→Ξ$^-$e$^+$ν$_e$)/BR(Ξ$_c^0$→Ξ$^-$π$^+$) = 1.38±0.14(stat)±0.22(syst) was measured with a total uncertainty reduced by a factor of about 3 with respect to the current world average reported by the Particle Data Group. The transverse momentum ($p_T$) dependence of the Ξ$_c^0-$ and Ξ$_c^+$-baryon production relative to the D$^0$ meson and to the Σ$_c^{0,+,++}$- and Λ$_c^+$-baryon production are reported. The baryon-to-meson ratio increases toward low $p_T$ up to a value of approximately 0.3. The measurements are compared with various models that take different hadronization mechanisms into consideration. The results provide stringent constraints to these theoretical calculations and additional evidence that different processes are involved in charm hadronization in electron-positron (e$^+$e$^-$) and hadronic collisions

Nuclear modification factor of light neutral-meson spectra up to high transverse momentum in p–Pb collisions at sNN=8.16 TeV

International audienceNeutral pion (π0) and η meson production cross sections were measured up to unprecedentedly high transverse momenta (pT) in p–Pb collisions at sNN=8.16TeV. The mesons were reconstructed via their two-photon decay channel in the rapidity interval −1.3&lt;y&lt;0.3 in the ranges of 0.4&lt;pT&lt;200 GeV/c and 1.0&lt;pT&lt;50 GeV/c, respectively. The respective nuclear modification factor (RpPb) is presented for pT up to of 200 and 30 GeV/c, where the former was achieved by extending the π0 measurement in pp collisions at s=8TeV using the merged cluster technique. The values of RpPb are below unity for pT&lt;10 GeV/c, while they are consistent with unity for pT&gt;10 GeV/c, leaving essentially no room for final state energy loss. The new data provide strong constraints for nuclear parton distribution and fragmentation functions over a broad kinematic range and are compared to model predictions as well as previous results at sNN=5.02TeV

Polarization of Λ and ¯Λ hyperons along the beam direction in Pb–Pb collisions at √sNN = 5.02 TeV

The polarization of the Λ and Λ¯¯¯¯ hyperons along the beam (z) direction, Pz, has been measured in Pb-Pb collisions at sNN−−−√ = 5.02TeV recorded with ALICE at the Large Hadron Collider (LHC). The main contribution to Pz comes from elliptic flow induced vorticity and can be characterized by the second Fourier sine coefficient Pz,s2=⟨Pzsin(2φ−2Ψ2)⟩, where φ is the hyperon azimuthal emission angle, and Ψ2 is the elliptic flow plane angle. We report the measurement of Pz,s2 for different collision centralities, and in the 30-50% centrality interval as a function of the hyperon transverse momentum and rapidity. The Pz,s2 is positive similarly as measured by the STAR Collaboration in Au-Au collisions at sNN−−−√ = 200 GeV, with somewhat smaller amplitude in the semi-central collisions. This is the first experimental evidence of a non-zero hyperon Pz in Pb-Pb collisions at the LHC. The comparison of the measured Pz,s2 with the hydrodynamic model calculations shows sensitivity to the competing contributions from thermal and the recently found shear induced vorticity, as well as to whether the polarization is acquired at the quark-gluon plasma or the hadronic phase