Morphine activates neuroinflammation in a manner parallel to endotoxin

Opioids create a neuroinflammatory response within the CNS, compromising opioid-induced analgesia and contributing to various unwanted actions. How this occurs is unknown but has been assumed to be via classic opioid receptors. Herein, we provide direct evidence that morphine creates neuroinflammation via the activation of an innate immune receptor and not via classic opioid receptors. We demonstrate that morphine binds to an accessory protein of Toll-like receptor 4 (TLR4), myeloid differentiation protein 2 (MD-2), thereby inducing TLR4 oligomerization and triggering proinflammation. Small-molecule inhibitors, RNA interference, and genetic knockout validate the TLR4/MD-2 complex as a feasible target for beneficially modifying morphine actions. Disrupting TLR4/MD-2 protein–protein association potentiated morphine analgesia in vivo and abolished morphine-induced proinflammation in vitro, the latter demonstrating that morphine-induced proinflammation only depends on TLR4, despite the presence of opioid receptors. These results provide an exciting, nonconventional avenue to improving the clinical efficacy of opioids.Xiaohui Wang, Lisa C. Loram, Khara Ramos, Armando J. de Jesus, Jacob Thomas, Kui Cheng, Anireddy Reddy, Andrew A. Somogyi, Mark R. Hutchinson, Linda R. Watkins and Hang Yi

A robust method for measurement of fluctuation parallel wavenumber in laboratory plasmas

Measuring the parallel wavenumber is fundamental for the experimental characterization of electrostatic instabilities. It becomes particularly important in toroidal geometry, where spatial inhomogeneities and curvature can excite both drift instabilities, whose wavenumber parallel to the magnetic field is finite, and interchange instabilities, which typically have vanishing parallel wavenumber. We demonstrate that multipoint measurements can provide a robust method for the discrimination between the two cases

Gapless finite-TT theory of collective modes of a trapped gas

We present predictions for the frequencies of collective modes of trapped Bose-condensed $^{87}$Rb atoms at finite temperature. Our treatment includes a self-consistent treatment of the mean-field from finite-$T$ excitations and the anomolous average. This is the first gapless calculation of this type for a trapped Bose-Einstein condensed gas. The corrections quantitatively account for the downward shift in the $m=2$ excitation frequencies observed in recent experiments as the critical temperature is approached.Comment: 4 pages Latex and 2 postscript figure

Limb bone scaling in hopping diprotodonts and quadrupedal artiodactyls

Bone adaptation is modulated by the timing, direction, rate, and magnitude of mechanical loads. To investigate whether frequent slow, or infrequent fast, gaits could dominate bone adaptation to load, we compared scaling of the limb bones from two mammalian herbivore clades that use radically different high-speed gaits, bipedal hopping and quadrupedal galloping. Forelimb and hindlimb bones were collected from 20 artiodactyl and 15 diprotodont species (body mass M 1.05 - 1536 kg) and scanned in clinical computed tomography or X-ray microtomography. Second moment of area (Imax) and bone length (l) were measured. Scaling relations (y = axb) were calculated for l vs M for each bone and for Imax vs M and Imax vs l for every 5% of length. Imax vs M scaling relationships were broadly similar between clades despite the diprotodont forelimb being nearly unloaded, and the hindlimb highly loaded, during bipedal hopping. Imax vs l and l vs M scaling were related to locomotor and behavioural specialisations. Low-intensity loads may be sufficient to maintain bone mass across a wide range of species. Occasional high-intensity gaits might not break through the load sensitivity saturation engendered by frequent low-intensity gaits

Excitations of a Bose-condensed gas in anisotropic traps

We investigate the zero-temperature collective excitations of a Bose-condensed atomic gas in anisotropic parabolic traps. The condensate density is determined by solving the Gross-Pitaevskii (GP) equation using a spherical harmonic expansion. The GP eigenfunctions are then used to solve the Bogoliubov equations to obtain the collective excitation frequencies and mode densities. The frequencies of the various modes, classified by their parity and the axial angular momentum quantum number, m, are mapped out as a function of the axial anisotropy. Specific emphasis is placed upon the evolution of these modes from the modes in the limit of an isotropic trap.Comment: 7 pages Revtex, 9 Postscript figure

Dissipation in nanocrystalline-diamond nanomechanical resonators

We have measured the dissipation and frequency of nanocrystalline-diamond nanomechanical resonators with resonant frequencies between 13.7 MHz and 157.3 MHz, over a temperature range of 1.4–274 K. Using both magnetomotive network analysis and a time-domain ring-down technique, we have found the dissipation in this material to have a temperature dependence roughly following T^(0.2), with Q^(–1) ≈ 10^(–4) at low temperatures. The frequency dependence of a large dissipation feature at ~35–55 K is consistent with thermal activation over a 0.02 eV barrier with an attempt frequency of 10 GHz