Clathrin-dependent endocytosis of membrane-bound RANKL in differentiated osteoclasts

Bone is continuously repaired and remodelled through well-coordinated activity of osteoblasts that form new bone and osteoclasts, which resorb it. Osteoblasts synthesize and secrete two key molecules that are important for osteoclast differentiation, namely the ligand for the receptor of activator of nuclear factor κB (RANKL) and its decoy receptor osteoprotegerin (OPG). Active membrane transport is a typical feature of the resorbing osteoclast during bone resorption. Normally, one resorption cycle takes several hours as observed by monitoring actin ring formation and consequent disappearance in vitro. During these cyclic changes, the cytoskeleton undergoes remarkable dynamic rearrangement. Active cells show a continuous process of exocytosis that plays an essential role in transport of membrane components, soluble molecules and receptor-mediated ligands thus allowing them to communicate with the environment. The processes that govern intracellular transport and trafficking in mature osteoclasts are poorly known. The principal methodological problem that have made these studies difficult is a physiological culture of osteoclasts that permit observing the vesicle apparatus in conditions similar to the in vivo conditions. In the present study we have used a number of morphological approaches to characterize the composition, formation and the endocytic and biosynthetic pathways that play roles in dynamics of differentiation of mature bone resorbing cells using a tri-dimensional system of physiologic coculture

Inhibition of bone resorption by Tanshinone VI isolated from Salvia miltiorrhiza Bunge

During the last decade, a more detailed knowledge of molecular mechanisms involved in osteoclastogenesis has driven research efforts in the development and screening of compound libraries of several small molecules that specifically inhibit the pathway involved in the commitment of the osteoclast precursor cells. Natural compounds that suppress osteoclast differentiation may have therapeutic value in treating osteoporosis and other bone erosive diseases such as rheumatoid arthritis or metastasis associated with bone loss. In ongoing investigation into anti-osteoporotic compounds from natural products we have analyzed the effect of Tanshinone VI on osteoclasts differentiation, using a physiologic three-dimensional osteoblast/bone marrow model of cell co-culture. Tanshinone VI is an abietane diterpene extracted from the root of Salvia miltiorrhiza Bunge (Labiatae), a Chinese traditional crude drug, “Tan-Shen”. Tashinone has been widely used in clinical practice for the prevention of cardiac diseases, arthritis and other inflammation-related disorders based on its pharmacological actions in multiple tissues. Although Tanshinone VI A has been used as a medicinal agent in the treatment of many diseases, its role in osteoclast-related bone diseases remains unknown. We showed previously that Tanshinone VI greatly inhibits osteoclast differentiation and suppresses bone resorption through disruption of the actin ring; subsequently, we intended to examine the precise inhibitory mechanism of Tanshinone VI on osteoclast differentiating factor. This study shows, for the first time, that Tanshinone VI prevents osteoclast differentiation by inhibiting RANKL expression and NFkB induction

Strain and correlation of self-organized Ge_(1-x)Mn_x nanocolumns embedded in Ge (001)

We report on the structural properties of Ge_(1-x)Mn_x layers grown by molecular beam epitaxy. In these layers, nanocolumns with a high Mn content are embedded in an almost-pure Ge matrix. We have used grazing-incidence X-ray scattering, atomic force and transmission electron microscopy to study the structural properties of the columns. We demonstrate how the elastic deformation of the matrix (as calculated using atomistic simulations) around the columns, as well as the average inter-column distance can account for the shape of the diffusion around Bragg peaks.Comment: 9 pages, 7 figure

Step by step capping and strain state of GaN/AlN quantum dots studied by grazing incidence diffraction anomalous fine structure

The investigation of small size embedded nanostructures, by a combination of complementary anomalous diffraction techniques, is reported. GaN Quantum Dots (QDs), grown by molecular beam epitaxy in a modified Stranski-Krastanow mode, are studied in terms of strain and local environment, as a function of the AlN cap layer thickness, by means of grazing incidence anomalous diffraction. That is, the X-ray photons energy is tuned across the Ga absorption K-edge which makes diffraction chemically selective. Measurement of \textit{hkl}-scans, close to the AlN (30-30) Bragg reflection, at several energies across the Ga K-edge, allows the extraction of the Ga partial structure factor, from which the in-plane strain of GaN QDs is deduced. From the fixed-Q energy-dependent diffracted intensity spectra, measured for diffraction-selected iso-strain regions corresponding to the average in-plane strain state of the QDs, quantitative information regarding composition and the out-of-plane strain has been obtained. We recover the in-plane and out-of-plane strains in the dots. The comparison to the biaxial elastic strain in a pseudomorphic layer indicates a tendency to an over-strained regime.Comment: submitted to PR

Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter

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The study of methane hydrate growth kinetics by NMR method

The nuclear magnetic resonance method conducted researches of longterm kinetics of growth of methane of hydrate on limit of the section gas - liquid (water). The amount of the formed methane of hydrate was registered according to the analysis of a signal of recession of a free induction. To methane to hydrate that part of a signal which was characterized by small time of a cross relaxation belonged. The analysis of kinetic curves of growth of thickness of a film of methane of hydrate on limit of the section gas-liquid showed that they aren't described within the assumption of normal diffusion of molecules of methane through a film of methane of hydrate. The detailed analysis of dependence of a share of a signal of methane of hydrate from time allows to suggest about abnormal diffusive process

High frequency magnetic oscillations of the organic metal θ\theta-(ET)4_4ZnBr4_4(C6_6H4_4Cl2_2) in pulsed magnetic field of up to 81 T

De Haas-van Alphen oscillations of the organic metal $\theta$-(ET)$_4$ZnBr$_4$(C$_6$H$_4$Cl$_2$) are studied in pulsed magnetic fields up to 81 T. The long decay time of the pulse allows determining reliable field-dependent amplitudes of Fourier components with frequencies up to several kiloteslas. The Fourier spectrum is in agreement with the model of a linear chain of coupled orbits. In this model, all the observed frequencies are linear combinations of the frequency linked to the basic orbit $\alpha$ and to the magnetic-breakdown orbit $\beta$.Comment: 6 pages, 4 figure

Analysis of strain and stacking faults in single nanowires using Bragg coherent diffraction imaging

Coherent diffraction imaging (CDI) on Bragg reflections is a promising technique for the study of three-dimensional (3D) composition and strain fields in nanostructures, which can be recovered directly from the coherent diffraction data recorded on single objects. In this article we report results obtained for single homogeneous and heterogeneous nanowires with a diameter smaller than 100 nm, for which we used CDI to retrieve information about deformation and faults existing in these wires. The article also discusses the influence of stacking faults, which can create artefacts during the reconstruction of the nanowire shape and deformation.Comment: 18 pages, 6 figures Submitted to New Journal of Physic