9,501 research outputs found

    Morphine activates neuroinflammation in a manner parallel to endotoxin

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    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

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    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

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    We present predictions for the frequencies of collective modes of trapped Bose-condensed 87^{87}Rb atoms at finite temperature. Our treatment includes a self-consistent treatment of the mean-field from finite-TT 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=2m=2 excitation frequencies observed in recent experiments as the critical temperature is approached.Comment: 4 pages Latex and 2 postscript figure

    Musculoskeletal modelling of an ostrich (Struthio camelus) pelvic limb: influence of limb orientation on muscular capacity during locomotion

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    We developed a three-dimensional, biomechanical computer model of the 36 major pelvic limb muscle groups in an ostrich (Struthio camelus) to investigate muscle function in this, the largest of extant birds and model organism for many studies of locomotor mechanics, body size, anatomy and evolution. Combined with experimental data, we use this model to test two main hypotheses. We first query whether ostriches use limb orientations (joint angles) that optimize the moment-generating capacities of their muscles during walking or running. Next, we test whether ostriches use limb orientations at mid-stance that keep their extensor muscles near maximal, and flexor muscles near minimal, moment arms. Our two hypotheses relate to the control priorities that a large bipedal animal might evolve under biomechanical constraints to achieve more effective static weight support. We find that ostriches do not use limb orientations to optimize the moment-generating capacities or moment arms of their muscles. We infer that dynamic properties of muscles or tendons might be better candidates for locomotor optimization. Regardless, general principles explaining why species choose particular joint orientations during locomotion are lacking, raising the question of whether such general principles exist or if clades evolve different patterns (e.g., weighting of muscle force–length or force–velocity properties in selecting postures). This leaves theoretical studies of muscle moment arms estimated for extinct animals at an impasse until studies of extant taxa answer these questions. Finally, we compare our model’s results against those of two prior studies of ostrich limb muscle moment arms, finding general agreement for many muscles. Some flexor and extensor muscles exhibit self-stabilization patterns (posture-dependent switches between flexor/extensor action) that ostriches may use to coordinate their locomotion. However, some conspicuous areas of disagreement in our results illustrate some cautionary principles. Importantly, tendon-travel empirical measurements of muscle moment arms must be carefully designed to preserve 3D muscle geometry lest their accuracy suffer relative to that of anatomically realistic models. The dearth of accurate experimental measurements of 3D moment arms of muscles in birds leaves uncertainty regarding the relative accuracy of different modelling or experimental datasets such as in ostriches. Our model, however, provides a comprehensive set of 3D estimates of muscle actions in ostriches for the first time, emphasizing that avian limb mechanics are highly three-dimensional and complex, and how no muscles act purely in the sagittal plane. A comparative synthesis of experiments and models such as ours could provide powerful synthesis into how anatomy, mechanics and control interact during locomotion and how these interactions evolve. Such a framework could remove obstacles impeding the analysis of muscle function in extinct taxa

    Dissipation in nanocrystalline-diamond nanomechanical resonators

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    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

    Excitation spectrum in a cylindrical Bose-Einstein gas

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    Whole excitation spectrum is calculated within the Popov approximation of the Bogoliubov theory for a cylindrical symmetric Bose-Einstein gas trapped radially by a harmonic potential. The full dispersion relation and its temperature dependence of the zero sound mode propagating along the axial direction are evaluated in a self-consistent manner. The sound velocity is shown to depend not only on the peak density, but also on the axial area density. Recent sound velocity experiment on Na atom gas is discussed in light of the present theory.Comment: 4 pages, 5 eps figure

    Are Fish Wild?

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    As the global biodiversity crisis continues, it is important to examine the legislative protection that is in place for species around the world. Such legislation not only includes environmental or wildlife law, but also trade law, such as the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), which gets transposed into national legislation. This commentary analyses legislative definitions of wildlife, whether or not that includes fish, which has implications for fish welfare, use of fish for food security, and biodiversity conservation when fish, or other wildlife, are excluded. Through a legislative content analysis of the 183 parties’ legislation of CITES, we explore whether fish are afforded the same protections as other species by being included in legal definitions of wildlife. We found that while a majority of CITES parties’ legislation appear to define fish as wildlife, there are a number of instances where this is unclear or not the case, and this could have significant ramifications for the welfare of non-human animals, their use, and conservation
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