Endocannabinoid regulation of amyloid-induced neuroinflammation

The modulation of endocannabinoid (EC) levels and the activation of cannabinoid receptors are seen as promising therapeutic strategies in a variety of diseases, including Alzheimer’s disease (AD). We aimed to evaluate the effect of the pharmacological and genetic inhibiton of anandamide (AEA)-degrading enzyme in a mouse model of AD (5xFAD). Pharmacological inhibition of the fatty acid amide hydrolase (FAAH) had little impact on the expression of key enzymes and cytokines as well as on the cognitive impairment and plaque deposition and gliosis in 5xFAD mice. CB1 blockade exacerbated inflammation in this transgenic mouse model of AD. The genetic inactivation of FAAH led to increases in the expression of inflammatory cytokines. At the same time, FAAH-null 5xFAD mice exhibited a behavioral improvement in spatial memory that was independent of the level of anxiety and was not CB1-mediated. Finally, mice lacking FAAH showed diminished soluble amyloid levels, neuritic plaques and gliosis. These data reinforce the notion of a role for the endocannabinoid system in neuroinflammation and open new perspectives on the relevance of modulating endocannabinoid levels in the inflammed brain.pre-print687 K

Cryopreservation Effect on Proliferative and Chondrogenic Potential of Human Chondrocytes Isolated from Superficial and Deep Cartilage

[Abstract] Objectives: To compare the proliferative and chondrogenic potential of fresh and frozen chondrocytes isolated from superficial and deep articular cartilage biopsies. Materials and Methodology: The study included 12 samples of fresh and frozen healthy human knee articular cartilage. Cell proliferation was tested at 3, 6 and 9 days. Studies of mRNA quantification, protein expression and immunofluorescence for proliferation and chondrogenic markers were performed. Results: Stimulation of fresh and frozen chondrocytes from both superficial and deep cartilage with fetal bovine serum produced an increase in the proliferative capacity compared to the non-stimulated control group. In the stimulated fresh cells group, the proliferative capacity of cells from the deep biopsy was greater than that from cells from the superficial biopsy (0.046 vs 0.028, respectively, p<0.05). There was also a significant difference between the proliferative capacity of superficial zone fresh (0.028) and frozen (0.051) chondrocytes (p<0.05). CCND1 mRNA and protein expression levels, and immunopositivity for Ki67 revealed a higher proliferative capacity for fresh articular chondrocytes from deep cartilage. Regarding the chondrogenic potential, stimulated fresh cells showed higher SOX9 and Col II expression in chondrocytes from deep than from superficial zone (p<0.05, T student test). Conclusions: The highest rate of cell proliferation and chondrogenic potential of fresh chondrocytes was found in cells obtained from deep cartilage biopsies, whereas there were no statistically significant differences in proliferative and chondrogenic capacity between biopsy origins with frozen chondrocytes. These results indicate that both origin and cryopreservation affect the proliferative and chondrogenic potential of chondrocytes.Servizo Galego de Saúde; PS07/84Instituto de Salud Carlos III; CIBER BBN CB06-01-0040Ministerio Ciencia e Innovacion; PLE2009-0144Ministerio Ciencia e Innovación; PI 08/202

Coherent J/ψ and ψ photoproduction at midrapidity in ultra-peripheral Pb–Pb collisions at √sNN = 5.02 TeV

The coherent photoproduction of J/ψJ/ψ and ψ′ψ′ mesons was measured in ultra-peripheral Pb–Pb collisions at a center-of-mass energy sNN−−−√ = 5.02sNN = 5.02 TeV with the ALICE detector. Charmonia are detected in the central rapidity region for events where the hadronic interactions are strongly suppressed. The J/ψJ/ψ is reconstructed using the dilepton (l+l−l+l−) and proton–antiproton decay channels, while for the ψ′ψ′ the dilepton and the l+l−π+π−l+l−π+π− decay channels are studied. The analysis is based on an event sample corresponding to an integrated luminosity of about 233 μb−1μb−1. The results are compared with theoretical models for coherent J/ψJ/ψ and ψ′ψ′ photoproduction. The coherent cross section is found to be in a good agreement with models incorporating moderate nuclear gluon shadowing of about 0.64 at a Bjorken-x of around 6×10−46×10−4, such as the EPS09 parametrization, however none of the models is able to fully describe the rapidity dependence of the coherent J/ψJ/ψ cross section including ALICE measurements at forward rapidity. The ratio of ψ′ψ′ to J/ψJ/ψ coherent photoproduction cross sections was also measured and found to be consistent with the one for photoproduction off protons.publishedVersio

Measurement of beauty and charm production in pp collisions at √s = 5.02 TeV via non-prompt and prompt D mesons

The pT-differential production cross sections of prompt and non-prompt (produced in beauty-hadron decays) D mesons were measured by the ALICE experiment at midrapidity (|y| < 0.5) in proton-proton collisions at s√s = 5.02 TeV. The data sample used in the analysis corresponds to an integrated luminosity of (19.3 ± 0.4) nb−1. D mesons were reconstructed from their decays D0 → K−π+, D+ → K−π+π+, and D+s→φπ+→K−K+π+Ds+→φπ+→K−K+π+ and their charge conjugates. Compared to previous measurements in the same rapidity region, the cross sections of prompt D+ and D+sDs+ mesons have an extended pT coverage and total uncertainties reduced by a factor ranging from 1.05 to 1.6, depending on pT, allowing for a more precise determination of their pT-integrated cross sections. The results are well described by perturbative QCD calculations. The fragmentation fraction of heavy quarks to strange mesons divided by the one to non-strange mesons, fs/(fu + fd), is compatible for charm and beauty quarks and with previous measurements at different centre-of-mass energies and collision systems. The bb¯¯¯bb¯ production cross section per rapidity unit at midrapidity, estimated from non-prompt D-meson measurements, is dσbb¯¯¯/dy∣∣|y|<0.5=34.5±2.4(stat)+4.7−2.9(tot.syst)dσbb¯/dy||y|<0.5=34.5±2.4(stat)−2.9+4.7(tot.syst) μb. It is compatible with previous measurements at the same centre-of-mass energy and with the cross section pre- dicted by perturbative QCD calculations.publishedVersio

Observation of a multiplicity dependence in the pT-differential charm baryon-to-meson ratios in proton–proton collisions at √ s = 13 TeV

The production of prompt D-0, D-s(+) and Lambda(+)(c) hadrons, and their ratios, D-s(+)/D-0 and Lambda(+)(c)/D-0, are measured in proton-proton collisions at root s = 13 TeV at midrapidity (vertical bar y vertical bar < 0.5) with the ALICE detector at the LHC. The measurements are performed as a function of the charm-hadron transverse momentum (p(T)) in intervals of charged-particle multiplicity, measured with two multiplicity estimators covering different pseudorapidity regions. While the strange to non-strange D-s(+)/D-0 ratio indicates no significant multiplicity dependence, the baryon-to-meson P-T-differential Lambda(+)(c)/D-0 ratio shows a multiplicity-dependent enhancement, with a significance of 5.3 sigma for 1 < p(T) < 12 GeV/c, comparing the highest multiplicity interval with respect to the lowest one. The measurements are compared with a theoretical model that explains the multiplicity dependence by a canonical treatment of quantum charges in the statistical hadronisation approach, and with predictions from event generators that implement colour reconnection mechanisms beyond the leading colour approximation to model the hadronisation process. The Lambda(+)(c)/D-0 ratios as a function of p(T) present a similar shape and magnitude as the Lambda/K-s(0) ratios in comparable multiplicity intervals, suggesting a potential common mechanism for light- and charmhadron formation, with analogous multiplicity dependence. The p(T)-integrated ratios, extrapolated down to p(T) = 0, do not show a significant dependence on multiplicity within the uncertainties. (C) 2022 European Organization for Nuclear Research. Published by Elsevier B.V

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

The 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 √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 (dNch/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 (dNch/dη/〈dNch/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 (〈pT〉) of J/ψ in pp collisions exhibits an increasing trend as a function of dNch/dη/〈dNch/dη〉 showing a saturation towards high charged-particle multiplicities

First study of the two-body scattering involving charm hadrons

This article presents the first measurement of the interaction between charm hadrons and nucleons. The two-particle momentum correlations of pD− and ¯pD+ pairs are measured by the ALICE Collaboration in high-multiplicity pp collisions at √s=13  TeV. The data are compatible with the Coulomb-only interaction hypothesis within (1.1–1.5)σ. The level of agreement slightly improves if an attractive nucleon (N)¯D strong interaction is considered, in contrast to most model predictions which suggest an overall repulsive interaction. This measurement allows for the first time an estimation of the 68% confidence level interval for the isospin I=0 inverse scattering length of the N¯D state f−10,I=0∈[−0.4,0.9]  fm−1, assuming negligible interaction for the isospin I=1 channel

First measurement of the |t|-dependence of coherent J/ψ photonuclear production

The first measurement of the cross section for coherent J/Psi photoproduction as a function of vertical bar t vertical bar, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb-Pbcollisions at a centre-of-mass energy per nucleon pair root s(NN) = 5.02 TeV with the J/Psi produced in the central rapidity region vertical bar y vertical bar < 0.8, which corresponds to the small Bjorken-xrange (0.3 - 1.4) x 10(-3). The measured vertical bar t vertical bar-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky-Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken- x. (C) 2021 The Author(s). Published by Elsevier B.V