Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes

Fine structure of the isoscalar giant quadrupole resonance in 40Ca due to Landau damping?

The fragmentation of the Isoscalar Giant Quadrupole Resonance (ISGQR) in 40Ca has been investigated in high energy-resolution experiments using proton inelastic scattering at E_p = 200 MeV. Fine structure is observed in the region of the ISGQR and its characteristic energy scales are extracted from the experimental data by means of a wavelet analysis. The experimental scales are well described by Random Phase Approximation (RPA) and second-RPA calculations with an effective interaction derived from a realistic nucleon-nucleon interaction by the Unitary Correlation Operator Method (UCOM). In these results characteristic scales are already present at the mean-field level pointing to their origination in Landau damping, in contrast to the findings in heavier nuclei and also to SRPA calculations for 40Ca based on phenomenological effective interactions, where fine structure is explained by the coupling to two-particle two-hole (2p-2h) states.Comment: Phys. Lett. B, in pres

Multiscale fluctuations in nuclear response

The nuclear collective response is investigated in the framework of a doorway picture in which the spreading width of the collective motion is described as a coupling to more and more complex configurations. It is shown that this coupling induces fluctuations of the observed strength. In the case of a hierarchy of overlapping decay channels, we observe Ericson fluctuations at different scales. Methods for extracting these scales and the related lifetimes are discussed. Finally, we show that the coupling of different states at one level of complexity to some common decay channels at the next level, may produce interference-like patterns in the nuclear response. This quantum effect leads to a new type of fluctuations with a typical width related to the level spacing.Comment: 34 Latex pages including 6 figures (submitted to Phys. Rev. C

Physiological and pathophysiological homeostasis of astroglial channel proteins by Nedd4-2

Nedd4-2 is an E3 ubiquitin ligase, missense mutation of which is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.1 (Kir4.1) and Connexin43 as Nedd4-2 substrates. We found that the expression of Kir4.1 and Connexin43 is increased upon conditional deletion of Nedd4-2 in astrocytes, leading to an elevation of astrocytic membrane ion permeability and gap junction activity, with a consequent reduction of γ-oscillatory neuronal network activity. Interestingly, our biochemical data demonstrate that missense mutations found in familial epileptic patients produce gain-of-function of Nedd4-2 gene product. Our data reveal a process of coordinated astrocytic ion channel proteostasis that controls astrocyte function and astrocyte-dependent neuronal network activity, and elucidate a potential mechanism by which aberrant Nedd4-2 function leads to epilepsy

Entry, Descent, and Landing with Propulsive Deceleration: Supersonic Retropropulsion Wind Tunnel Testing and Shock Phenomena

The future exploration of the Solar System will require innovations in transportation and the use of entry, descent, and landing (EDL) systems at many planetary landing sites. The cost of space missions has always been prohibitive, and using the natural planetary and planet's moon atmospheres for entry, and descent can reduce the cost, mass, and complexity of these missions. This paper will describe some of the EDL ideas for planetary entry and survey the overall technologies for EDL that may be attractive for future Solar System missions. Future EDL systems may include an inflatable decelerator for the initial atmospheric entry and an additional supersonic retropropulsion (SRP) rocket system for the final soft landing. A three engine retropropulsion configuration with a 2.5 in. diameter sphere-cone aeroshell model was tested in the NASA Glenn Research Center's 1- by 1-ft (11) Supersonic Wind Tunnel (SWT). The testing was conducted to identify potential blockage issues in the tunnel, and visualize the rocket flow and shock interactions during supersonic and hypersonic entry conditions. Earlier experimental testing of a 70deg Viking-like (sphere-cone) aeroshell was conducted as a baseline for testing of a SRP system. This baseline testing defined the flow field around the aeroshell and from this comparative baseline data, retropropulsion options will be assessed. Images and analyses from the SWT testing with 300- and 500-psia rocket engine chamber pressures are presented here. In addition, special topics of electromagnetic interference with retropropulsion induced shock waves and retropropulsion for Earth launched booster recovery are also addressed

Effects of wall cooling and leading-edge blunting on ramp-induced, laminar flow separations at Mach numbers from 3 through 6 /

The effects of wall cooling and nose bluntness on laminar and transitional reattaching flows induced by a 9.5-degree ramp were investigated at Mach numbers from 3 through 6 measuring the longitudinal surface pressure and heat-transfer rate distributions, as well as the flow-field pressures, at several longitudinal stations. Reynolds number based on flat-plate length was varied from 0.25 to 1.0 million. The trend in the change in interaction length with Reynolds number increase indicated laminar reattachment at all test Reynolds numbers at M = 6 and transitional at the two higher Reynolds numbers at M = 3.Report was prepared by ARO, Inc., a subsidiary of Sverdrup & Parcel and Associates, Inc."Final ReportNovember 30, 1970, to April 16, 1971.""March 1972."Includes bibliographic references (page 83).The effects of wall cooling and nose bluntness on laminar and transitional reattaching flows induced by a 9.5-degree ramp were investigated at Mach numbers from 3 through 6 measuring the longitudinal surface pressure and heat-transfer rate distributions, as well as the flow-field pressures, at several longitudinal stations. Reynolds number based on flat-plate length was varied from 0.25 to 1.0 million. The trend in the change in interaction length with Reynolds number increase indicated laminar reattachment at all test Reynolds numbers at M = 6 and transitional at the two higher Reynolds numbers at M = 3.Mode of access: Internet