The effects of amino-acid mutations on specific interactions between urokinase-type plasminogen activator and its receptor: Ab initio molecular orbital calculations

During cancer invasion, the binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) on the surface of a cancer cell is considered a trigger for invasion. Here, we present a stable structure of the solvated complex formed between uPA and uPAR (uPA-uPAR) and investigate the specific interactions between uPA and uPAR by ab initio fragment molecular orbital (FMO) calculations. The result indicates that the electrostatic interactions between the charged amino acid residues existing in both uPA and uPAR make a large contribution to the binding between uPA and uPAR. In particular, Lys23, Lys46, Lys98 and Lys61 of uPA are found to have strong attractive interactions with uPAR. To elucidate the effect of these residues on the interactions between uPA and uPAR, we substituted each of them with the uncharged amino acid Leu and investigated the interactions between the mutated uPA and wild-type uPAR. The interaction energies indicate that Lys46 and Lys98, which bind uPA to the rim of the central ligand-binding cavity of uPAR, make greater contributions to the binding between uPA and uPAR than Lys23, which is positioned at the bottom of the ligand-binding cavity of uPAR. The effect of hydrating water molecules located between uPA and uPAR is also investigated to be significant for the specific interactions between uPA and uPAR. These results are expected to be informative for developing new peptide antagonists that block the binding of uPA to uPAR.     

Synthesis of polyamide-hydroxyapatite nanocomposites

Simultaneous one-pot syntheses of PA66 and HAp were carried out by extracting H₂O and CO₂ from PA66 monomers and HAp raw materials, respectively, resulting in the formation of a polyamide (PA) 66-hydroxyapatite (HAp) nanocomposite. During the process, a spherical nano-sized HAp particle was precipitated following dissolution of micro-sized CaHPO₄・2H₂O. The PA66 monomers were subsequently adsorbed onto the generated HAp product. Some of the adsorbed PA66 monomers formed a bound polymer on HAp, and an increase in the adhesiveness of the PA66-HAp interface was observed as the polymerization progressed. During this process, the synthesis of a nanocomposite from a micro-sized raw material and creation of an autonomous strong interface between the matrix and filler was achieved. In addition, the shape of the resultant HAp was controllable and could be modified to needle shape by the addition of F⁻ and Mg²⁺ ions to the raw material. HAp could also be changed to plate shape via octa-calcium phosphate (OCP). Notably, during the synthesis, the filler shape of the nanocomposite could be controlled to 0D (particle), 1D (needle), and 2D (plate).     

Space charge field effect on light emitting from tetracene field-effect transistor under AC electric field

By applying square wave AC voltage to the Au source electrode of tetracene based field-effect transistor (FET), electroluminescence (EL) was obtained. The results suggest that electrons and holes were injected alternately from the source electrode and recombined each other, and lead to the EL. This type of EL was localized at the interface between the source electrode and tetracene, and enhanced periodically with two relaxation times in accordance with the applied AC voltage cycle. We modeled the carrier behavior in the FET and explained the decay of EL, taking into account the space charge field contribution. Finally, using an AC voltage superposed on DC bias voltage, it was shown that electron injection was prompted only by space charge field.     

Fine TiC dispersed Al2O3 composites fabricated via in situ reaction synthesis and conventional process

To further improve the mechanical performance and reduce the percolation threshold by controlling microstructures, Al₂O₃-TiC composites containing 0-20 vol% TiC were fabricated via in situ reaction synthesis. Graphite (ATC) and carbon nanotubes (ATCT) were used as carbon sources. The composites were also fabricated via a conventional process using a TiC starting powder (AT). X-ray diffraction analysis and scanning electron microscopy observation results indicated successful fabrication of the composites with various microstructures. TiC particles in ATCT were completely dispersed at grain boundaries, whereas in ATC and AT, these particles were either intragranular or intergranular dispersed. The composites could be listed as follows, ATCT > ATC > AT, that is, in descending order of the reinforcing flexural strength and fracture toughness. The nanoindentation measurement indicated the optimum hardening effect of ATCT. The ATCT composite also exhibited the highest fracture toughness, which was 49% higher than that of the monolithic Al₂O₃. Crack deflection was considered as the main toughening mechanism while crack bridging behavior also occurred in ATCT. For a given TiC content, ATCT exhibited the lowest electrical resistivity, owing mainly to the complete grain-boundary dispersion of the relatively large TiC particles. The similarity of the Al₂O₃ grain size and TiC particle size of ATCT contributed to the lowest percolation threshold achieved (11.2%), which (to date) is the lowest value that has been reported for the Al₂O₃-TiC system.     

Solid polymerization and supramolecular chirality formation of azobenzene substituted diacetylene Langmuir–Blodgett films

An azobenzene mesogen-substituted diacetylene (NADA) monolayer has been transferred onto the solid substrate by the traditional Langmuir–Blodgett (LB) method. Solid-state polymerization of NADA LB films can be sensitized in visible light region. In situ UV–vis absorption measurement enables us to study polymerization kinetics of NADA LB films. The polymerization process can be described as a first order rate equation and polymerization rate constants are characterized in detail. Furthermore, achiral NADA molecules can form chiral LB films through overcrowded packing of the azobenzene moiety.     

Effects of glucagon on glycogenolysis and gluconeogenesis are region-specific in periportal and perivenous hepatocytes

BACKGROUND: Survival of post-myocardial infarction patients is related inversely to their levels of very-low-frequency (0.003 to 0.03 Hz) RR-interval variability. The physiological basis for such oscillations is unclear. In our study, we used blocking drugs to evaluate potential contributions of sympathetic and vagal mechanisms and the renin-angiotensin-aldosterone system to very-low-frequency RR-interval variability in 10 young healthy subjects. METHODS AND RESULTS: We recorded RR intervals and arterial pressures during three separate sessions, with the patient in supine and 40 degree upright tilt positions, during 20-minute frequency (0.25 Hz) and tidal volume-controlled breathing after intravenous injections: saline (control), atenolol (0.2 mg/kg, beta-adrenergic blockade), atropine sulfate (0.04 mg/kg, parasympathetic blockade), atenolol and atropine (complete autonomic blockade), and enalaprilat (0.02 mg/kg, ACE blockade). We integrated fast Fourier transform RR-interval spectral power at very low (0.003 to 0.03 Hz), low (0.05 to 0. 15 Hz), and respiratory (0.2 to 0.3 Hz) frequencies. Beta-adrenergic blockade had no significant effect on very-low- or low-frequency RR-interval power but increased respiratory frequency power 2-fold. ACE blockade had no significant effect on low or respiratory frequency RR-interval power but modestly (approximately 21%) increased very-low-frequency power in the supine (but not upright tilt) position (P<0.05). The most profound effects were exerted by parasympathetic blockade: Atropine, given alone or with atenolol, abolished nearly all RR-interval variability and decreased very-low-frequency variability by 92%. CONCLUSIONS: Although very-low-frequency heart period rhythms are influenced by the renin-angiotensin-aldosterone system, as low and respiratory frequency RR-interval rhythms, they depend primarily on the presence of parasympathetic outflow. Therefore the prognostic value of very-low-frequency heart period oscillations may derive from the fundamental importance of parasympathetic mechanisms in cardiovascular health.     

Domain observation and molecular orientation of chiral dipalmitoylphosphatidylcholine monolayer by Brewster angle microscopy and Maxwell displacement current

To understand the relationship between molecular chirality and electrical properties of monolayers, Maxwell displacement current (MDC) behaviors and domain shapes of chiral DPPC monolayers composed of dextro- (d-) and levo- (l-) rotatory molecules at the air-water interface are investigated during monolayer compression using MDC measurement and the Brewster angle microscopy (BAM) system. The experimental results show that for DPPC monolayers of the two pure enantiomers, the π-A isotherms and the MDC behaviors are similar to each other, while the domain patterns of them are mirror shapes of different sizes. This reveals that MDC behaviors due to molecular spontaneous polarization have no relation to chirality but domain shapes closely depend on the molecular chirality. Moreover, the observed domain shapes verify the domain shape theory which was recently developed by Iwamoto et al. [M. Iwamoto, Z.C. Ou-Yang, Phy. Rev. Letts, 93 (2004) 206101].