1,720,974 research outputs found
Water dynamics in dilute aqueous solutions of small apolar solutes by quasi-elastic neutron scattering
No full textRigid molecule approximation in memory function-based models for molecular liquids : Application to liquid water
No full textPressure effect on water dynamics in tert-butyl alcohol/water solutions
No full textWe report here a quasi-elastic neutron scattering (QENS) investigation of the effect of pressure on the diffusivity properties of water in a dilute aqueous solution of hydrophobic molecules (tert-butyl alcohol, TBA). The experiment was performed at fixed TBA concentration (0.02 molar fraction) by varying pressure from 1 to 2000 bar at two different temperatures (268 and 278 K). The quasi-elastic line-shapes have been analysed in terms of a model based on the memory function formalism. Our data indicate that, on increasing pressure up to 2000 bar, the diffusion coefficient of water in the TBA/water mixture exhibits a relative increase larger than that of pure water under the same thermodynamic conditions. The extent of this effect increases with decreasing temperature. The observed behaviour is described in terms of pressure-induced distortions of the H-bonded random network of liquid water
Structural biology of cisplatin complexes with cellular targets: the adduct with human copper chaperone Atox1 in aqueous solution
No full textCisplatin is one of the most used anticancer drugs. Its cellular influx and delivery to target DNA may involve the copper chaperone Atox1 protein. Although the mode of binding is established by NMR spectroscopy measurements in solution-the Pt atom binds to Cys12 and Cys15 while retaining the two ammine groups-the structural determinants of the adduct are not known. Here a structural model by hybrid Car-Parrinello density functional theory-based QM/MM simulations is provided. The platinated site minimally modifies the fold of the protein. The calculated NMR and CD spectral properties are fully consistent with the experimental data. Our in silico/in vitro approach provides, together with previous studies, an unprecedented view into the structural biology of cisplatin-protein adducts
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Platination of the copper transporter ATP7A involved in anticancer drug resistance
No full textThe clinical efficacy of the widely used anticancer drug cisplatin is severely limited by the emergence of resistance. This is related to the drug binding to proteins such as the copper influx transporter Ctr1, the copper chaperone Atox1, and the copper pumps ATP7A and ATP7B. While the binding modes of cisplatin to the first two proteins are known, the structural determinants of platinated ATP7A/ATP7B are lacking. Here we investigate the interaction of cisplatin with the first soluble domain of ATP7A. First, we establish by ESI-MS and (1)H, (13)C, and (15)N NMR that, in solution, the adduct is a monomer in which the sulfur atoms of residues Cys19 and Cys22 are cis-coordinated to the [Pt(NH3)2](2+) moiety. Then, we carry out hybrid Car-Parrinello QM/MM simulations and computational spectroscopy calculations on a model adduct based on the NMR structure of the apo protein and featuring the experimentally determined binding mode of the metal ion. These calculations show quantitative agreement with CD spectra and (1)H, (13)C, and (15)N NMR chemical shifts, thus providing a quantitative molecular view of the 3D binding mode of cisplatin to ATP7A. Importantly, the same comparison rules out a variety of alternative models with different coordination modes, that we explored to test the robustness of the computational approach. Using this combined in silico-in vitro approach we provide here for the first time a quantitative 3D atomic view of the platinum binding to the first soluble domain of ATP7A
Diffusive dynamics of water in tert-butyl alcohol/water mixtures
No full textQuasielastic neutron scattering has been used to investigate the dynamical behavior of H2O in water/tert-butyl alcohol solutions. The measurements were made at fixed temperature (293 K) as a function of tert-butyl alcohol molar fraction, x, in the range 0–0.042. The data have been compared to those of pure water in the temperature range 269–293 K. The effect of tert-butyl alcohol addition on water dynamics is equivalent to that obtained by lowering the temperature of pure water by an amount proportional to the alcohol concentration. The temperature dependence of the diffusivity parameters in pure water and their concentration dependence in tert-butyl alcohol/water solutions can be rescaled to a common curve attributing to each solution a concentration-dependent “structural temperature” lower than the actual thermodynamic one. These results can be understood in terms of Stillinger’s picture of water structuring and of other more recent theoretical pictures that emphasize the influence of the geometrical properties of hydrogen bond networks on water mobility
Lecithin-chitosan nanoparticles for the transmucosal delivery of progesterone via chimerical agglomerates
No full textSmall angle scattering investigation of chitosan/lecithin nanoparticles, potential carriers for drug delivery
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