Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Saturn Atmospheric Structure and Dynamics

2 Saturn inhabits a dynamical regime of rapidly rotating, internally heated atmospheres similar to Jupiter. Zonal winds have remained fairly steady since the time of Voyager except in the equatorial zone and slightly stronger winds occur at deeper levels. Eddies supply energy to the jets at a rate somewhat less than on Jupiter and mix potential vorticity near westward jets. Convective clouds exist preferentially in cyclonic shear regions as on Jupiter but also near jets, including major outbreaks near 35°S associated with Saturn electrostatic discharges, and in sporadic giant equatorial storms perhaps generated from frequent events at depth. The implied meridional circulation at and below the visible cloud tops consists of upwelling (downwelling) at cyclonic (anti-cyclonic) shear latitudes. Thermal winds decay upward above the clouds, implying a reversal of the circulation there. Warm-core vortices with associated cyclonic circulations exist at both poles, including surrounding thick high clouds at the south pole. Disequilibrium gas concentrations in the tropical upper troposphere imply rising motion there. The radiative-convective boundary and tropopause occur at higher pressure in the southern (summer) hemisphere due to greater penetration of solar heating there. A temperature “knee ” of warm air below the tropopause, perhaps due to haze heating, is stronger in the summer hemisphere as well. Saturn’s south polar stratosphere is warmer than predicted by radiative models and enhanced in ethane, suggesting subsidence-driven adiabatic warming there. Recent modeling advances suggest that shallow weather laye