Skin electrical activity of the stomach and intestine during long-term antiorthostatic hypokinesia

The skin electrical activity of the gastrointestinal tract in the stomach and small intestine frequency ranges was studied for four months in 13 men under the conditions of antiorthostatic hypokinesia (AOH). On an empty stomach, both the gastric and small intestine electrical activities increased to a level comparable with that of the increase detectable after eating under the conditions of normal motor activity, whereas the response to food stimulation was inhibited. The ratios between the parameters of spectral analysis testified to a higher tonic component in the stomach and a higher peristaltic component in the intestine under the conditions of AOH. The observed changes in the gastric and intestinal electrical activities were observed against a background of a hypersecretory state of the stomach and an increase in the intestinal contents. During the readaptation period, both the gastric and intestinal electrical activities increased significantly, whereas the response to food stimulation was inhibited.     

The three-dimensional structure of the antigen-binding fragment of a monoclonal antibody to human interleukin-2 in two crystal forms at 2.2 and 2.9 Å resolution

The three-dimensional structure of the antigen-binding fragment of a monoclonal antibody to human interleukin-2 was determined in two crystal forms by the X-ray method of molecular replacement at 2.2 and 2.9 Å resolutions. The spatial structure of the protein and the stereochemistry of its antigen-binding site were analyzed.     

Perfusion protection of ischemic liver using perfluorocarbon emulsion

Several concentrations of Fluorocarbon emulsion as means for anti-ischemic protection of the liver were studied in experiments on 47 rabbits with hypothermic perfusion of isolated liver exposed to 90 minute ischaemia. the best concentration of Fluorocarbon emulsion for perfusion of isolated liver was 12%.     

Impact of temperature on Na2Sr(PO4)F:Eu3+ phosphor

In this article, we report the synthesis of Na₂Sr_1‐x(PO₄)F:Eu_x phosphor via a combustion method. The influence of different annealing temperatures on the photoluminescence properties was investigated. The phosphor was excited at both 254 and 393 nm. Na₂Sr_1‐x(PO₄)F:Eu_x³⁺ phosphors emit strong orange and red color at 593 and 612 nm, respectively, under both excitation wavelengths. Na₂Sr_1‐x(PO₄)F:Eu_x³⁺ phosphors annealed at 1050°C showed stronger emission intensity compared with 600, 900 and 1200°C. Moreover, Na₂Sr_1‐x(PO₄)F:Eu_x³⁺ phosphor was found to be more intense when compared with commercial Y₂O₃:Eu³⁺ phosphor. Copyright © 2013 John Wiley & Sons, Ltd.     

Structural Role of the Conserved Cysteines in the Dimerization of the Viral Transmembrane Oncoprotein E5

The E5 oncoprotein is the major transforming protein of bovine papillomavirus type 1. This 44-residue transmembrane protein can interact with the platelet-derived growth factor receptor β, leading to ligand-independent activation and cell transformation. For productive interaction, E5 needs to dimerize via a C-terminal pair of cysteines, though a recent study suggested that its truncated transmembrane segment can dimerize on its own. To analyze the structure of the full protein in a membrane environment and elucidate the role of the Cys-Ser-Cys motif, we produced recombinantly the wild-type protein and four cysteine mutants. Comparison by circular dichroism in detergent micelles and lipid vesicular dispersion and by NMR in trifluoroethanol demonstrates that the absence of one or both cysteines does not influence the highly α-helical secondary structure, nor does it impair the ability of E5 to dimerize, observations that are further supported by sodium dodecylsulfate polyacrylamide gel electrophoresis. We also observed assemblies of higher order. Oriented circular dichroism in lipid bilayers shows that E5 is aligned as a transmembrane helix with a slight tilt angle, and that this membrane alignment is also independent of any cysteines. We conclude that the Cys-containing motif represents a disordered region of the protein that serves as an extra covalent connection for stabilization.     

Experimental investigation of X-ray lasing in a capillary argon discharge

Results are presented from experiments on the laser generation of X-ray radiation at the wavelength λ=469 ? (ε=26.4 eV) on the 3p(J=0)−3s(J=1) transition of Ne-like Ar ions. Experiments were carried out on the SIGNAL electrophysical facility with a 3.1-mm-diameter 157-mm-long Al₂O₃ ceramic capillary filled with argon at a pressure of 0.2–1.0 Torr. The discharge current amplitude was I ∼ 25–40 kA, the current rise rate being dI/dt ∼ 10¹² A/s. By a vacuum X-ray diode tuned to detect X-ray photons with energies in the range 10–40 eV, laser pulses with a duration of t ₁ ∼ 1 ns and maximum energy of E _1,max ∼ 1 μJ were recorded. The pulses were generated 35 ns after the discharge current was switched on. The line spectra in the wavelength range of 150–500 ? showed the bright λ=469 ? line. The angular divergence of the generated X-ray laser beam was estimated to be Δϑ ∼ 2 mrad. Original Russian Text ? O.N. Gilev, V.I. Afonin, V.I. Ostashev, V.Yu. Politov, A.M. Gafarov, A.L. Zapysov, A.V. Andriyash, é.P. Magda, L.N. Shamraev, A.A. Safronov, A.V. Komissarov, N.A. Khavronin, N.A. Pkhaĭko, L.V. Antonova, L.N. Shushlebin, 2006, published in Fizika Plazmy, 2006, Vol. 32, No. 2, pp. 160–165.     

Hydrophobic matching controls the tilt and stability of the dimeric platelet-derived growth factor receptor (PDGFR) β transmembrane segment

The platelet-derived growth factor receptor β is a member of the cell surface receptor tyrosine kinase family and dimerizes upon activation. We determined the structure of the transmembrane segment in dodecylphosphocholine micelles by liquid-state NMR and found that it forms a stable left-handed helical dimer. Solid-state NMR and oriented circular dichroism were used to measure the tilt angle of the helical segments in macroscopically aligned model membranes with different acyl chain lengths. Both methods showed that decreasing bilayer thickness (DEPC-POPC-DMPC) led to an increase in the helix tilt angle from 10° to 30° with respect to the bilayer normal. At the same time, reconstitution of the comparatively long hydrophobic segment became less effective, eventually resulting in complete protein aggregation in the short-chain lipid DLPC. Unrestrained molecular dynamics simulations of the dimer were carried out in explicit lipid bilayers (DEPC, POPC, DMPC, sphingomyelin), confirming the observed dependence of the helix tilt angle on bilayer thickness. Notably, molecular dynamics revealed that the left-handed dimer gets tilted en bloc, whereas conformational transitions to alternative (e.g. right-handed dimeric) states were not supported. The experimental data along with the simulation results demonstrate a pronounced interplay between the platelet-directed growth factor receptor β transmembrane segment and the bilayer thickness. The effect of hydrophobic mismatch might play a key role in the redistribution and activation of the receptor within different lipid microdomains of the plasma membrane in vivo.     

Secretory activity of the stomach during modeling of enhanced filling of abdominal veins

Determination of the secretory activity of the stomach and ultrasound scanning of human gastroduodenal organs and vessels in experiments with −12° and −15° head-down tilting (HDT) hypokinesia were performed. As a result of short-term (12–24 h) HDT hypokinesia with the minimized hypokinesia factor, parenchymatous organs enlarged, and the walls of hollow organs thickened. Enhanced blood filling of abdominal veins was accompanied by elevated pepsinogen levels in blood and urine and increased gastric contents in fasting subjects. The increased tonicity of the pylorus and the delayed evacuation of stomach contents indicated the activation of hydrochloric acid secretion. Simultaneously, the bile and pancreatic juice were secreted more profusely, and the intestinal contents in the duodenum increased. It has been shown that the modeled enhancement of blood filling of abdominal veins stimulates gastric secretion on an empty stomach, which is accompanied by activation of secretion in the liver and pancreas.     

Design and self-assembly of siRNA-functionalized RNA nanoparticles for use in automated nanomedicine

Individual genes can be targeted with siRNAs. The use of nucleic acid nanoparticles (NPs) is a convenient method for delivering combinations of specific siRNAs in an organized and programmable manner. We present three assembly protocols to produce two different types of RNA self-assembling functional NPs using processes that are fully automatable. These NPs are engineered based on two complementary nanoscaffold designs (nanoring and nanocube), which serve as carriers of multiple siRNAs. The NPs are functionalized by the extension of up to six scaffold strands with siRNA duplexes. The assembly protocols yield functionalized RNA NPs, and we show that they interact in vitro with human recombinant Dicer to produce siRNAs. Our design strategies allow for fast, economical and easily controlled production of endotoxin-free therapeutic RNA NPs that are suitable for preclinical development.