Non-Peptide Opioids Differ in Effects on Mu-Opioid (MOP) and Serotonin 1A (5-HT1A) Receptors Heterodimerization and Cellular Effectors (Ca2+, ERK1/2 and p38) Activation

The importance of the dynamic interplay between the opioid and the serotonin neuromodulatory systems in chronic pain is well recognized. In this study, we investigated whether these two signalling pathways can be integrated at the single-cell level via direct interactions between the mu-opioid (MOP) and the serotonin 1A (5-HT_1A) receptors. Using fluorescence cross-correlation spectroscopy (FCCS), a quantitative method with single-molecule sensitivity, we characterized in live cells MOP and 5-HT_1A interactions and the effects of prolonged (18 h) exposure to selected non-peptide opioids: morphine, codeine, oxycodone and fentanyl, on the extent of these interactions. The results indicate that in the plasma membrane, MOP and 5-HT_1A receptors form heterodimers that are characterized with an apparent dissociation constant Kdapp = (440 ± 70) nM). Prolonged exposure to all non-peptide opioids tested facilitated MOP and 5-HT_1A heterodimerization and stabilized the heterodimer complexes, albeit to a different extent: Kd, Fentanylapp = (80 ± 70) nM), Kd,Morphineapp = (200 ± 70) nM, Kd, Codeineapp = (100 ± 70) nM and Kd, Oxycodoneapp = (200 ± 70) nM. The non-peptide opioids differed also in the extent to which they affected the mitogen-activated protein kinases (MAPKs) p38 and the extracellular signal-regulated kinase (Erk1/2), with morphine, codeine and fentanyl activating both pathways, whereas oxycodone activated p38 but not ERK1/2. Acute stimulation with different non-peptide opioids differently affected the intracellular Ca²⁺ levels and signalling dynamics. Hypothetically, targeting MOP–5-HT_1A heterodimer formation could become a new strategy to counteract opioid induced hyperalgesia and help to preserve the analgesic effects of opioids in chronic pain.     

On stochastic mixing caused by the Rayleigh-Taylor instability

The mixing of contacting substances is considered. The evolution of the mixing layer over a long time period from multimode initial perturbations is investigated numerically in the short-scale and wide-range cases. In the case of a short-scale initiation, the flow is stochastic in the sense that the time of the considered evolution exceeds the period of correlation. The effect of the amplitude of wide-range perturbations on the dynamics of mixing is analyzed. The scale-invariant properties of the spectral and statistical parameters of turbulent mixing are investigated for the first time. The universal spectra characterizing the turbulence mixing in the entire self-similar interval on a unified basis are obtained. The simulation is based on the effective algorithms with high approximating qualities, which have been tested earlier.     

Amphiphilic Invertible Polyesters as Reducing and Stabilizing Agents in the Formation of Metal Nanoparticles

Metal nanoparticles of various size and shape are prepared by the reduction of metal precursors in polymer micellar architectures (nanoreactors). The nanoreactors are developed from the amphiphilic invertible polyesters solved over a wide concentration range in solvents that strongly differ in polarity. In a non‐polar medium, the micelle core contains hydrophilic [poly(ethylene oxide)] fragments, which acts as a reducing agent of metal ions. Nanoparticle stabilization occurs because of the presence of hydrophobic (polymethylene) fragments outside of the micelle structure. The size and shape of the nanoreactors may be altered by the polyester composition and molecular weight as well as by the solvent polarity and concentration of the amphiphilic polyester.

     

A selective catalytic side chain oxidation of lysine and ornithine derivatives

The fully protected derivatives of the diamino acids lysine and ornithine (n=1, 2) can be oxidized selectively in the side chain using a Mn(OAc)₂/peracetic acid/NaOAc system. The ε or γ carbon, respectively, is converted to the aldehyde oxidation state, protected as the cyclic N,N-acetal.     

Bias of LS estimators in nonlinear regression models with constraints. Part I: General Case

We derive expressions for the asymptotic approximation of the bias of the least squares estimators in nonlinear regression models with parameters which are subject to nonlinear equality constraints.The approach suggested modifies the normal equations of the estimator, and approximates them up to o _p(N ^–1), where N is the number of observations. The bias equations so obtained are solved under different assumptions on constraints and on the model. For functions of the parameters the invariance of the approximate bias with respect to reparametrisations is demonstrated. Singular models are considered as well, in which case the constraints may serve either to identify the parameters, or eventually to restrict the parameter space.     

Temperature dependence of the 1J(11B19F) spin–spin coupling in BF3 molecule

The ¹J(¹¹B¹⁹F) spin–spin coupling of gaseous BF₃ was observed in ¹¹B NMR spectra as a function of density in a wide range of temperatures. Following the extrapolation of the measured values to the zero‐density limit, the coupling constant free from intermolecular effects ¹J₀(¹¹B¹⁹F) was obtained for each temperature. In contrast to previous investigations, the final results indicate a nonlinear dependence of ¹J₀(¹¹B¹⁹F) on temperature. In the corresponding ab initio calculations of spin–spin coupling constants performed at the coupled cluster singles and doubles (CCSD) level to obtain a reliable result for this coupling constant we had to take into account large vibrational corrections. Copyright © 2009 John Wiley & Sons, Ltd.     

Wavelet expansion of functions on a differentiable manifold

A wavelet expansion involving uniform meshes is accounted in many of the references (see, e.g., [1–4] and references therein); results on wavelets on nonuniform meshes may be found in [5–8]. Numerical flows associated with a smooth manifold may be processed using local functions (see [9]). However, development of efficient algorithms involves the resources of wavelet expansions.     

Studies of CoQ10 and cyclodextrin complexes: solubility, thermo- and photo-stability

The complexes of coenzyme Q10 with β- and γ-cyclodextrin in aqueous solutions were prepared in order to improve the water solubility, thermo- and photo-stability of coenzyme Q10. Complex formation resulted in an increase in water solubility at room temperature and pH 6.5 by a factor at least 10². The solubility of coenzyme Q10 in the presence of cyclodextrins linearly increases with temperature and pH. The UV light (λ = 254) and temperature together have a great effect on coenzyme Q10 stability. After 120 min of exposure at 80 °C and UV light about 72.3% of pure coenzyme Q10 was degraded. Thermo- and photo-stability was strongly improved by complex formation; more than 64% of coenzyme Q10 remained unchanged. The formation of complexes was evaluated using IR spectrometry, X-ray diffractometry and TGA/DSC analysis.