609 research outputs found

    Cerebrospinal fluid, brain, and spinal cord levels of L-aspartate signal excitatory neurotransmission abnormalities in multiple sclerosis patients and experimental autoimmune encephalomyelitis mouse model

    Get PDF
    The neuroinflammatory process characterizing multiple sclerosis (MS) is associated with changes in excitatory synaptic transmission and altered central concentrations of the primary excitatory amino acid, L-glutamate (L-Glu). Recent findings report that cerebrospinal fluid (CSF) levels of L-Glu positively correlate with pro-inflammatory cytokines in MS patients. However, to date, there is no evidence about the relationship between the other primary excitatory amino acid, L-aspartate (L-Asp), its derivative D-enantiomer, D-aspartate, and the levels of pro-inflammatory and anti-inflammatory cytokines in the CSF of MS. In the present study, we measured by HPLC the levels of these amino acids in the cortex, hippocampus, cerebellum, and spinal cord of mice affected by experimental autoimmune encephalomyelitis (EAE). Interestingly, in support of glutamatergic neurotransmission abnormalities in neuroinflammatory conditions, we showed reduced L-Asp levels in the cortex and spinal cord of EAE mice and increased D-aspartate/total aspartate ratio within the cerebellum and spinal cord of these animals. Additionally, we found significantly decreased CSF levels of L-Asp in both relapsing-remitting (n = 157) MS (RR-MS) and secondary progressive/primary progressive (n = 22) (SP/PP-MS) patients, compared to control subjects with other neurological diseases (n = 40). Importantly, in RR-MS patients, L-Asp levels were correlated with the CSF concentrations of the inflammatory biomarkers G-CSF, IL-1ra, MIP-1ÎČ, and Eotaxin, indicating that the central content of this excitatory amino acid, as previously reported for L-Glu, reflects a neuroinflammatory environment in MS. In keeping with this, we revealed that CSF L-Asp levels were positively correlated with those of L-Glu, highlighting the convergent variation of these two excitatory amino acids under inflammatory synaptopathy occurring in MS

    Towards a muon collider

    Get PDF
    A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work

    The population of merging compact binaries inferred using gravitational waves through GWTC-3

    Get PDF
    We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 Gpc−3yr−1\rm{Gpc^{-3} yr^{-1}} and 1700 Gpc−3yr−1\rm{Gpc^{-3} yr^{-1}} and the NSBH merger rate to be between 7.8 Gpc−3 yr−1\rm{Gpc^{-3}\, yr^{-1}} and 140 Gpc−3yr−1\rm{Gpc^{-3} yr^{-1}} , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 Gpc−3 yr−1\rm{Gpc^{-3}\, yr^{-1}} and 44 Gpc−3 yr−1\rm{Gpc^{-3}\, yr^{-1}} at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from 1.2−0.2+0.1M⊙1.2^{+0.1}_{-0.2} M_\odot to 2.0−0.3+0.3M⊙2.0^{+0.3}_{-0.3} M_\odot. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 M⊙M_\odot. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above ∌60M⊙\sim 60 M_\odot. The rate of BBH mergers is observed to increase with redshift at a rate proportional to (1+z)Îș(1+z)^{\kappa} with Îș=2.9−1.8+1.7\kappa = 2.9^{+1.7}_{-1.8} for zâ‰Č1z\lesssim 1. Observed black hole spins are small, with half of spin magnitudes below χi≃0.25\chi_i \simeq 0.25. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio

    Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV