648 research outputs found
Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory
Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimerâs disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory
Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory
Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimerâs disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory
Disrupted iron regulation in the brain and periphery in cocaine addiction
Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery. We determined iron concentration in the brain, using quantitative susceptibility mapping, and in the periphery, using iron markers in circulating blood, in 44 patients with cocaine addiction and 44 healthy controls. Cocaine-addicted individuals showed excess iron accumulation in the globus pallidus, which strongly correlated with duration of cocaine use, and mild iron deficiency in the periphery, which was associated with low iron levels in the red nucleus. Our findings show that iron dysregulation occurs in cocaine addiction and suggest that it arises consequent to chronic cocaine use. Putamen enlargement in these individuals was unrelated to iron concentrations, suggesting that these are co-occurring morphological changes that may respectively reflect predisposition to, and consequences of cocaine addiction. Understanding the mechanisms by which cocaine affects iron metabolism may reveal novel therapeutic targets, and determine the value of iron levels in the brain and periphery as biomarkers of vulnerability to, as well as progression and response to treatment of cocaine addiction
HLA-A and -B alleles and haplotypes in hemochromatosis probands with HFE C282Y homozygosity in central Alabama
BACKGROUND: We wanted to quantify HLA-A and -B allele and haplotype frequencies in Alabama hemochromatosis probands with HFE C282Y homozygosity and controls, and to compare results to those in other populations. METHODS: Alleles were detected using DNA-based typing (probands) and microlymphocytotoxicity (controls). RESULTS: Alleles were determined in 139 probands (1,321 controls) and haplotypes in 118 probands (605 controls). In probands, A*03 positivity was 0.7482 (0.2739 controls; p =< 0.0001; odds ratio (OR) 7.9); positivity for B*07, B*14, and B*56 was also increased. In probands, haplotypes A*03-B*07 and A*03-B*14 were more frequent (p < 0.0001, respectively; OR = 12.3 and 11.1, respectively). The haplotypes A*01-B*60, A*02-B*39, A*02-B*62, A*03-B*13, A*03-B*15, A*03-B*27, A*03-B*35, A*03-B*44, A*03-B*47, and A*03-B*57 were also significantly more frequent in probands. 37.3% of probands were HLA-haploidentical with other proband(s). CONCLUSIONS: A*03 and A*03-B*07 frequencies are increased in Alabama probands, as in other hemochromatosis cohorts. Increased absolute frequencies of A*03-B*35 have been reported only in the present Alabama probands and in hemochromatosis patients in Italy. Increased absolute frequencies of A*01-B*60, A*02-B*39, A*02-B*62, A*03-B*13, A*03-B*15, A*03-B*27, A*03-B*44, A*03-B*47, and A*03-B*57 in hemochromatosis cohorts have not been reported previously
Measurement of and binding energy in Au+Au collisions at = 3 GeV
Measurements of mass and binding energy of and
in Au+Au collisions at GeV are
presented, with an aim to address the charge symmetry breaking (CSB) problem in
hypernuclei systems with atomic number A = 4. The binding energies
are measured to be MeV and MeV for and , respectively. The measured binding-energy difference
is MeV for ground states. Combined with
the -ray transition energies, the binding-energy difference for excited
states is MeV, which is negative and
comparable to the value of the ground states within uncertainties. These new
measurements on the binding-energy difference in A = 4 hypernuclei
systems are consistent with the theoretical calculations that result in
and present a new method for the study of CSB effect using relativistic
heavy-ion collisions.Comment: 8 pages, 5 figure
Search for a common baryon source in high-multiplicity pp collisions at the LHC
We report on the measurement of the size of the particle-emitting source from two-baryon correlations with ALICE in high-multiplicity pp collisions at s=13 TeV. The source radius is studied with low relative momentum pâp, pâŸâpâŸ, pâÎ, and pâŸâÎ⟠pairs as a function of the pair transverse mass mT considering for the first time in a quantitative way the effect of strong resonance decays. After correcting for this effect, the radii extracted for pairs of different particle species agree. This indicates that protons, antiprotons, Î s, and Î⟠s originate from the same source. Within the measured mT range (1.1â2.2) GeV/c2the invariant radius of this common source varies between 1.3 and 0.85 fm. These results provide a precise reference for studies of the strong hadronâhadron interactions and for the investigation of collective properties in small colliding systems. © 2020 CERN for the benefit of the ALICE CollaborationPeer reviewe
Inclusive J/Ï production at forward and backward rapidity in p-Pb collisions at âsNN=8.16 TeV
Inclusive J/psi production is studied in p-Pb interactions at a centre-of-mass
energy per nucleon-nucleon collision sqrt(s_NN) = 8.16TeV, using the ALICE detector at the
CERN LHC. The J/psi meson is reconstructed, via its decay to a muon pair, in the centre-of-mass
rapidity intervals 2.03 < ycms < 3.53 and -4.46 < ycms < -2.96, where positive
and negative ycms refer to the p-going and Pb-going direction, respectively. The transverse
momentum coverage is pT < 20 GeV/c. In this paper, ycms- and pT-differential cross
sections for inclusive J/psi production are presented, and the corresponding nuclear modification
factors RpPb are shown. Forward results show a suppression of the J/psi yield with
respect to pp collisions, concentrated in the region pT < 5 GeV/c. At backward rapidity
no significant suppression is observed. The results are compared to previous measurements
by ALICE in p-Pb collisions at sqrt(s_NN) = 5.02TeV and to theoretical calculations. Finally,
the ratios RFB between forward- and backward-ycms RpPb values are shown and discussed
Global baryon number conservation encoded in net-proton fluctuations measured in PbâPb collisions at âsNN = 2.76 TeV
Experimental results are presented on event-by-event net-proton fluctuation measurements in PbâPb collisions at âSNN=2.76 TeV, recorded by the ALICE detector at the CERN LHC. These measurements have as their ultimate goal an experimental test of Lattice QCD (LQCD) predictions on second and higher order cumulants of net-baryon distributions to search for critical behavior near the QCD phase boundary. Before confronting them with LQCD predictions, account has to be taken of correlations stemming from baryon number conservation as well as fluctuations of participating nucleons. Both effects influence the experimental measurements and are usually not considered in theoretical calculations. For the first time, it is shown that event-by-event baryon number conservation leads to subtle long-range correlations arising from very early interactions in the collisions.publishedVersio
Evidence of Spin-Orbital Angular Momentum Interactions in Relativistic Heavy-Ion Collisions
The first evidence of spin alignment of vector mesons (K^{*0} and Ï) in heavy-ion collisions at the Large Hadron Collider (LHC) is reported. The spin density matrix element Ï_{00} is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at a center-of-mass energy (sqrt[s_{NN}]) of 2.76Â TeV with the ALICE detector. Ï_{00} values are found to be less than 1/3 (1/3 implies no spin alignment) at low transverse momentum (p_{T}<2ââGeV/c) for K^{*0} and Ï at a level of 3Ï and 2Ï, respectively. No significant spin alignment is observed for the K_{S}^{0} meson (spin=0) in Pb-Pb collisions and for the vector mesons in pp collisions. The measured spin alignment is unexpectedly large but qualitatively consistent with the expectation from models which attribute it to a polarization of quarks in the presence of angular momentum in heavy-ion collisions and a subsequent hadronization by the process of recombination
- âŠ