CCR5 limits cortical viral loads during West Nile virus infection of the central nervous system

BACKGROUND: Cell-mediated immunity is critical for clearance of central nervous system (CNS) infection with the encephalitic flavivirus, West Nile virus (WNV). Prior studies from our laboratory have shown that WNV-infected neurons express chemoattractants that mediate recruitment of antiviral leukocytes into the CNS. Although the chemokine receptor, CCR5, has been shown to play an important role in CNS host defense during WNV infection, regional effects of its activity within the infected brain have not been defined. METHODS: We used CCR5-deficient mice and an established murine model of WNV encephalitis to determine whether CCR5 activity impacts on WNV levels within the CNS in a region-specific fashion. Statistical comparisons between groups were made with one- or two-way analysis of variance; Bonferroni’s post hoc test was subsequently used to compare individual means. Survival was analyzed by the log-rank test. Analyses were conducted using Prism software (GraphPad Prism). All data were expressed as means ± SEM. Differences were considered significant if P ≤ 0.05. RESULTS: As previously shown, lack of CCR5 activity led to increased symptomatic disease and mortality in mice after subcutaneous infection with WNV. Evaluation of viral burden in the footpad, draining lymph nodes, spleen, olfactory bulb, and cerebellum derived from WNV-infected wild-type, and CCR5(−/−) mice showed no differences between the genotypes. In contrast, WNV-infected, CCR5(−/−) mice exhibited significantly increased viral burden in cortical tissues, including the hippocampus, at day 8 post-infection. CNS regional studies of chemokine expression via luminex analysis revealed significantly increased expression of CCR5 ligands, CCL4 and CCL5, within the cortices of WNV-infected, CCR5(−/−) mice compared with those of similarly infected WT animals. Cortical elevations in viral loads and CCR5 ligands in WNV-infected, CCR5(−/−) mice, however, were associated with decreased numbers of infiltrating mononuclear cells and increased permeability of the blood-brain barrier. CONCLUSIONS: These data indicate that regional differences in chemokine expression occur in response to WNV infection of the CNS, and that cortical neurons require CCR5 activity to limit viral burden in this brain region

Nucleation and Growth of the Superconducting Phase in the Presence of a Current

We study the localized stationary solutions of the one-dimensional time-dependent Ginzburg-Landau equations in the presence of a current. These threshold perturbations separate undercritical perturbations which return to the normal phase from overcritical perturbations which lead to the superconducting phase. Careful numerical work in the small-current limit shows that the amplitude of these solutions is exponentially small in the current; we provide an approximate analysis which captures this behavior. As the current is increased toward the stall current J*, the width of these solutions diverges resulting in widely separated normal-superconducting interfaces. We map out numerically the dependence of J* on u (a parameter characterizing the material) and use asymptotic analysis to derive the behaviors for large u (J* ~ u^-1/4) and small u (J -> J_c, the critical deparing current), which agree with the numerical work in these regimes. For currents other than J* the interface moves, and in this case we study the interface velocity as a function of u and J. We find that the velocities are bounded both as J -> 0 and as J -> J_c, contrary to previous claims.Comment: 13 pages, 10 figures, Revte

Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review

Dislocation-induced superfluidity in a model supersolid

Motivated by recent experiments on the supersolid behavior of $^4$He, we study the effect of an edge dislocation in promoting superfluidity in a Bose crystal. Using Landau theory, we couple the elastic strain field of the dislocation to the superfluid density, and use a linear analysis to show that superfluidity nucleates on the dislocation before occurring in the bulk of the solid. Moving beyond the linear analysis, we develop a systematic perturbation theory in the weakly nonlinear regime, and use this method to integrate out transverse degrees of freedom and derive a one-dimensional Landau equation for the superfluid order parameter. We then extend our analysis to a network of dislocation lines, and derive an XY model for the dislocation network by integrating over fluctuations in the order parameter. Our results show that the ordering temperature for the network has a sensitive dependence on the dislocation density, consistent with numerous experiments that find a clear connection between the sample quality and the supersolid response.Comment: 10 pages, 6 figure

Scaling Relations of Viscous Fingers in Anisotropic Hele-Shaw Cells

Viscous fingers in a channel with surface tension anisotropy are numerically studied. Scaling relations between the tip velocity v, the tip radius and the pressure gradient are investigated for two kinds of boundary conditions of pressure, when v is sufficiently large. The power-law relations for the anisotropic viscous fingers are compared with two-dimensional dendritic growth. The exponents of the power-law relations are theoretically evaluated.Comment: 5 pages, 4 figure

Flux penetration in slab shaped Type-I superconductors

We study the problem of flux penetration into type--I superconductors with high demagnetization factor (slab geometry).Assuming that the interface between the normal and superconducting regions is sharp, that flux diffuses rapidly in the normal regions, and that thermal effects are negligible, we analyze the process by which flux invades the sample as the applied field is increased slowly from zero.We find that flux does not penetrate gradually.Rather there is an instability in the process and the flux penetrates from the boundary in a series of bursts, accompanied by the formation of isolated droplets of the normal phase, leading to a multiply connected flux domain structure similar to that seen in experiments.Comment: 4 pages, 2 figures, Fig 2.(b) available upon request from the authors, email - [email protected]

Deployable-erectable trade study for space station truss structures

The results of a trade study on truss structures for constructing the space station are presented. Although this study was conducted for the reference gravity gradient space station, the results are generally applicable to other configurations. The four truss approaches for constructing the space station considered in this paper were the 9 foot single fold deployable, the 15 foot erectable, the 10 foot double fold tetrahedral, and the 15 foot PACTRUSS. The primary rational for considering a 9 foot single-fold deployable truss (9 foot is the largest uncollapsed cross-section that will fit in the Shuttle cargo bay) is that of ease of initial on-orbit construction and preintegration of utility lines and subsystems. The primary rational for considering the 15 foot erectable truss is that the truss bay size will accommodate Shuttle size payloads and growth of the initial station in any dimension is a simple extension of the initial construction process. The primary rational for considering the double-fold 10 foot tetrahedral truss is that a relatively large amount of truss structure can be deployed from a single Shuttle flight to provide a large number of nodal attachments which present a pegboard for attaching a wide variety of payloads. The 15 foot double-fold PACTRUSS was developed to incorporate the best features of the erectable truss and the tetrahedral truss

Vortex Pull by an External Current

In the context of a dynamical Ginzburg-Landau model it is shown numerically that under the influence of a homogeneous external current J the vortex drifts against the current with velocity $V= -J$ in agreement to earlier analytical predictions. In the presence of dissipation the vortex undergoes skew deflection at an angle $90^{\circ} < \delta < 180^{\circ}$ with respect to the external current. It is shown analytically and verified numerically that the angle $\delta$ and the speed of the vortex are linked through a simple mathematical relation.Comment: 19 pages, LATEX, 6 Postscript figures included in separate compressed fil

Metals and Bacteria Partitioning to Various Size Particles in Ballona Creek Storm Water Runoff

Many storm water best management practice (BMP) devices function primarily by capturing particulate matter to take advantage of the well‐documented association between storm water particles and pollutants. The hydrodynamic separation or settling methods used by most BMP devices are most effective at capturing medium to large particles; however, these may not be the most predominant particles associated with urban runoff. The present study examined particle size distribution in storm water runoff from an urban watershed in southern California and investigated the pollutant–particle associations of metals (Cu, Pb, Ni, and Zn) and bacteria (enterococci and Escherichia coli). During small storm events (≤0.7 cm rain), the highest concentration of pollutants were associated with a \u3c6‐µm filter fraction, which accounted for 70% of the per storm contaminant mass but made up more than 20% of the total particle mass. The pollutant–particle association changed with storm size. Most pollutant mass was associated with \u3e35 µm size particles during a 5‐cm rain event. These results suggest that much of the contaminant load in storm water runoff will not be captured by the most commonly used BMP devices, because most of these devices (e.g., hydrodynamic separators) are unable to capture particles smaller than 75 µm