39 research outputs found
Aspartoacylase-LacZ Knockin Mice: An Engineered Model of Canavan Disease
Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. The neurological phenotypes of different rodent models of CD vary considerably. Here we report on a novel targeted aspa mouse mutant expressing the bacterial β-Galactosidase (lacZ) gene under the control of the aspa regulatory elements. X-Gal staining in known ASPA expression domains confirms the integrity of the modified locus in heterozygous aspa lacZ-knockin (aspalacZ/+) mice. In addition, abundant ASPA expression was detected in Schwann cells. Homozygous (aspalacZ/lacZ) mutants are ASPA-deficient, show CD-like histopathology and moderate neurological impairment with behavioural deficits that are more pronounced in aspalacZ/lacZ males than females. Non-invasive ultrahigh field proton magnetic resonance spectroscopy revealed increased levels of NAA, myo-inositol and taurine in the aspalacZ/lacZ brain. Spongy degeneration was prominent in hippocampus, thalamus, brain stem, and cerebellum, whereas white matter of optic nerve and corpus callosum was spared. Intracellular vacuolisation in astrocytes coincides with axonal swellings in cerebellum and brain stem of aspalacZ/lacZ mutants indicating that astroglia may act as an osmolyte buffer in the aspa-deficient CNS. In summary, the aspalacZ mouse is an accurate model of CD and an important tool to identify novel aspects of its complex pathology
Optimization of momentum imaging systems using electric and magnetic field
International audienc
Double photoionization of H2S below the double ionization potential
International audienc
The umbrella motion of core-excited CH3 and CD3 methyl radicals
An accurate experimental and theoretical study of the lowest core excitation of CH3 and CD3 methyl
radicals is presented. The complex vibrational structure of the lowest band of the x-ray absorption
spectrum XAS is due to the large variation of the molecular geometry, which is planar in the
ground state and pyramidal in the core-excited state. The XAS spectra of the two radicals were
recorded at high resolution and assigned by theoretical simulations of the spectra, taking into
account the coupling of symmetrical stretching and symmetrical bending umbrellalike
deformations of the radicals. An excellent agreement between experimental and theoretical spectral
profiles allowed us to accurately characterize the vibrational structure of the electronic transition.
The similarities, as well as the differences, of the peculiar vibrational progression observed for the
two radicals are explained by the strong anharmonicity along the umbrella coordinate and by the
isotopic variation, leading to a different probing of the double-well potential energy surface of the
core excited state during the nuclear motion
Interplay between Electronic and Nuclear Motion in the Photodouble Ionization of H2
International audienc
Probing the potential energy surface by high-resolution x-ray absorption spectroscopy: The umbrella motion of the core-excited CH3 free radical
A detailed study of the umbrellalike vibration in inner-shell spectroscopy is presented. The high-resolution
x-ray absorption spectrum for the lowest lying core excitation of the CH3 free radical was recorded. High
quality potential energy surfaces PES for the initial and final states of the transition were calculated as a
function of the symmetrical stretching and the umbrella deformation coordinates. The strong anharmonicity
along the umbrella coordinate in the double-well region of the PES of the core excited state has a strong effect
on the bending vibrational progressions. The excellent agreement between the experiment and theory allows an
accurate spectroscopic characterization of the vibrational structure of the electronic transition, and the estimation
of the umbrella inversion time of 149 fs