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

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

Expression of target and reference genes in Daphnia magna exposed to ibuprofen

Background: Transcriptomic techniques are now being applied in ecotoxicology and toxicology to measure the impact of stressors and develop understanding of mechanisms of toxicity. Microarray technology in particular offers the potential to measure thousands of gene responses simultaneously. However, it is important that microarrays responses should be validated, at least initially, using real-time quantitative polymerase chain reaction (QPCR). The accurate measurement of target gene expression requires normalisation to an invariant internal control e. g., total RNA or reference genes. Reference genes are preferable, as they control for variation inherent in the cDNA synthesis and PCR. However, reference gene expression can vary between tissues and experimental conditions, which makes it crucial to validate them prior to application. Results: We evaluated 10 candidate reference genes for QPCR in Daphnia magna following a 24 h exposure to the non-steroidal anti-inflammatory drug (NSAID) ibuprofen (IB) at 0, 20, 40 and 80 mg IB l(-1). Six of the 10 candidates appeared suitable for use as reference genes. As a robust approach, we used a combination normalisation factor (NF), calculated using the geNorm application, based on the geometric mean of three selected reference genes: glyceraldehyde-3-phosphate dehydrogenase, ubiquitin conjugating enzyme and actin. The effects of normalisation are illustrated using as target gene leukotriene B4 12-hydroxydehydrogenase (Ltb4dh), which was upregulated following 24 h exposure to 63-81 mg IB l(-1). Conclusions: As anticipated, use of the NF clarified the response of Ltb4dh in daphnids exposed to sublethal levels of ibuprofen. Our findings emphasise the importance in toxicogenomics of finding and applying invariant internal QPCR control(s) relevant to the study conditions

Bivariate tt-distribution for transition matrix elements in Breit-Wigner to Gaussian domains of interacting particle systems

Interacting many-particle systems with a mean-field one body part plus a chaos generating random two-body interaction having strength $\lambda$, exhibit Poisson to GOE and Breit-Wigner (BW) to Gaussian transitions in level fluctuations and strength functions with transition points marked by $\lambda=\lambda_c$ and $\lambda=\lambda_F$, respectively; $\lambda_F >> \lambda_c$. For these systems theory for matrix elements of one-body transition operators is available, as valid in the Gaussian domain, with $\lambda > \lambda_F$, in terms of orbitals occupation numbers, level densities and an integral involving a bivariate Gaussian in the initial and final energies. Here we show that, using bivariate $t$-distribution, the theory extends below from the Gaussian regime to the BW regime up to $\lambda=\lambda_c$. This is well tested in numerical calculations for six spinless fermions in twelve single particle states.Comment: 7 pages, 2 figure

Kinetic Theory of Collective Excitations and Damping in Bose-Einstein Condensed Gases

We calculate the frequencies and damping rates of the low-lying collective modes of a Bose-Einstein condensed gas at nonzero temperature. We use a complex nonlinear Schr\"odinger equation to determine the dynamics of the condensate atoms, and couple it to a Boltzmann equation for the noncondensate atoms. In this manner we take into account both collisions between noncondensate-noncondensate and condensate-noncondensate atoms. We solve the linear response of these equations, using a time-dependent gaussian trial function for the condensate wave function and a truncated power expansion for the deviation function of the thermal cloud. As a result, our calculation turns out to be characterized by two dimensionless parameters proportional to the noncondensate-noncondensate and condensate-noncondensate mean collision times. We find in general quite good agreement with experiment, both for the frequencies and damping of the collective modes.Comment: 10 pages, 8 figure

Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific

Background: In a mammalian host, the cell surface of African trypanosomes is protected by a monolayer of a single variant surface glycoprotein (VSG). The VSG is central to antigenic variation; one VSG gene is expressed at any one time and there is a low frequency stochastic switch to expression of a different VSG gene. The genome of Trypanosoma brucei contains a repertoire of > 1000 VSG sequences. The degree of conservation of the genomic VSG repertoire in different strains has not been investigated in detail.|Results: Eighteen expressed VSGs from Ugandan isolates were compared with homologues (> 40 % sequence identity) in the two available T. brucei genome sequences. Fourteen homologues were present in the genome of Trypanosoma brucei brucei TREU927 from Kenya and fourteen in the genome of T. b. gambiense Dal972 from Cote d'Ivoire. The Ugandan VSGs averaged 71% and 73 % identity to homologues in T. b. brucei and T. b. gambiense respectively. The sequence divergence between homologous VSGs from the three different strains was not random but was more prevalent in the parts of the VSG believed to interact with the host immune system on the living trypanosome.|Conclusion: It is probable that the VSG repertoires in the different isolates contain many common VSG genes. The location of divergence between VSGs is consistent with selection for strain-specific VSG repertoires, possibly to allow superinfection of an animal by a second strain. A consequence of strain-specific VSG repertoires is that any vaccine based on large numbers of VSGs from a single strain will only provide partial protection against other strains

Strongly Non-Equilibrium Bose-Einstein Condensation in a Trapped Gas

We present a qualitative (and quantitative, at the level of estimates) analysis of the ordering kinetics in a strongly non-equilibrium state of a weakly interacting Bose gas, trapped with an external potential. At certain conditions, the ordering process is predicted to be even more rich than in the homogeneous case. Like in the homogeneous case, the most characteristic feature of the full-scale non-equilibrium process is the formation of superfluid turbulence.Comment: 4 pages, revtex, no figures. Submitted to PR

Finite-temperature simulations of the scissors mode in Bose-Einstein condensed gases

The dynamics of a trapped Bose-condensed gas at finite temperatures is described by a generalized Gross-Pitaevskii equation for the condensate order parameter and a semi-classical kinetic equation for the thermal cloud, solved using $N$-body simulations. The two components are coupled by mean fields as well as collisional processes that transfer atoms between the two. We use this scheme to investigate scissors modes in anisotropic traps as a function of temperature. Frequency shifts and damping rates of the condensate mode are extracted, and are found to be in good agreement with recent experiments.Comment: 4 pages, 3 figure

Spherical probes at ion saturation in E × B fields

The ion saturation current to a spherical probe in the entire range of ion magnetization is computed with SCEPTIC3D, a newthree-dimensional version of the kinetic code SCEPTIC designed to study transverse plasma flows. Results are compared with prior two-dimensional calculations valid in the magneticfree regime (Hutchinson 2002 Plasma Phys. Control. Fusion 44 1953), and with recent semi-analytic solutions to the strongly magnetized transverse Mach probe problem (Patacchini and Hutchinson 2009 Phys. Rev. E 80 036403). At intermediate magnetization (ion Larmor radius close to the probe radius) the plasma density profiles show a complex three-dimensional structure that SCEPTIC3D can fully resolve, and, contrary to intuition, the ion current peaks provided the ion temperature is low enough. Our results are conveniently condensed in a single factor M[subscript c], function of ion temperature and magnetic field only, providing the theoretical calibration for a transverse Mach probe with four electrodes placed at 45◦ to the magnetic field in a plane of flow and magnetic field