Hepatitis C virus utilizes lipid droplet for production of infectious virus

Hepatitis C virus (HCV) establishes a persistent infection and causes chronic hepatitis. Chronic hepatitis patients often develop hepatic cirrhosis and progress to liver cancer. The development of this pathological condition is linked to the persistent infection of the virus. In other words, viral replication/multiplication may contribute to disease pathology. Accumulating clinical studies suggest that HCV infection alters lipid metabolism, and thus causes fatty liver. It has been reported that this abnormal metabolism exacerbates hepatic diseases. Recently, we revealed that lipid droplets play a key role in HCV replication. Understanding the molecular mechanism of HCV replication will help elucidate the pathogenic mechanism and develop preventive measures that inhibit disease manifestation by blocking persistent infection. In this review, we outline recent findings on the function of lipid droplets in the HCV replication cycle and describe the relationship between the development of liver diseases and virus replication.     

Improvement of depth resolution in XPS analysis of fluorinated layer using C60 ion sputtering

Depth profile of C₆₀ ion-used X-ray photoelectron spectroscopy (XPS) was studied on fluorinated organic layers with different thicknesses. We found that the depth resolution decreased, the sputtering rate went down and the surface turned rough as the layer thickness increased. This is because carbon-rich layer was formed on the surface by cross-linking reaction of the polymer and/or accumulation of degraded C₆₀ through continuous sputtering. Surprisingly, the high sputtering rate drastically improved the resolution of the analysis. The rate over 48.7 nm/min did not show any deterioration on the depth resolution, the sputtering rate and surface smoothness.     

Indoline derivatives I: synthesis and factor Xa (FXa) inhibitory activities

A series of bisamidine derivatives each having a ring structure in the center of the molecule was synthesized and their Factor Xa (FXa) inhibitory activities were evaluated. Among them, some indoline derivatives showed potent inhibitory activities in vitro. In particular, (R)-18a having an (R)-configuration at the 2-position of the indoline ring exhibited the most potent FXa inhibitory activity in vitro, more potent than DX-9065a. Furthermore, (R)-18a exhibited more potent anticoagulant activity than DX-9065a. We also succeeded in obtaining an X-ray crystal structure of FXa bound with (R)-18a.     

Carboxyfluorescein leakage from poly(ethylene glycol)-grafted liposomes induced by the interaction with serum

The effects of fetal bovine serum (FBS) on carboxyfluorescein (CF) leakage from poly(ethylene glycol)-grafted liposomes (PEG-liposomes) were investigated. PEG-liposomes were prepared from dipalmitoylphosphatidylcholine (DPPC) and distearoyl-N-monomethoxy poly(ethylene glycol)-succinyl-phosphatidylethanolamines (DSPE-PEG) having PEG molecular weights of 1000, 2000, 3000 and 5000. The presence of FBS dramatically increased CF leakage from liposomes near the gel-liquid crystalline phase transition temperature, but had little effect at lower and higher temperatures. The CF leakage from PEG-liposomes whose molecular weight in PEG units was above 2000 was suppressed compared with that of liposomes without PEG. And, there was hardly any difference in the effect of the PEG molecular weight of the PEG-lipids on CF leakage from PEG-liposomes with FBS when PEG-lipids with a molecular weight in PEG units above 2000 were used. On the other hand, the leakage of CF from liposomes containing 0.145 mol fractions of DSPE-PEG1000 was larger than that of liposomes without PEG. Furthermore, the effects of FBS on the cooperative units of lipid molecules during the gel-liquid crystalline phase transition of liposomes were examined. However, the cooperative units of liposomes with FBS had little change compared with that of liposomes without FBS.     

Thermal rectification in nonmetallic solid junctions: Effect of Kapitza resistance

Based on Fourier's law for heat conduction, we investigate the asymmetric heat flow in two segment rods of nonmetallic materials. Specifically, we study the effect of the Kapitza resistance at the boundary of the segments on the thermal rectification. To understand basic features of the rectification, we first develop analytical calculation for the heat currents in an ideal rod of a macroscopic length. Explicitly, this is made by assuming that the thermal conductivity of each constituent has a power-law dependence on temperature and also assuming the continuity of temperature at the boundary. Then, we introduce the temperature jump at the boundary due to the Kapitza resistance and show that this effect on the thermal rectification becomes significant as the length of the rod decreases typically to submillimeters. In particular, we find that the temperature jump yields a finite rectification even when no asymmetry is predicted in the heat currents from the continuity of temperature at the junction. The obtained results have an important implication for the analysis of the thermal rectification of a rod consisting of semiconductors Ge and Si.     

A regularity criterion to the biharmonic map heat flow in ℜ4

We consider the regularity problem under the critical condition to the biharmonic map heat flow from ?⁴ to a smooth compact Riemannian manifold without boundary. Using Gagliardo‐Nirenberg inequalities and delicate estimates, the Serrin type regularity criterion for the smooth solutions of biharmonic map heat flow is obtained without assuming a smallness condition on the initial energy. Our result improved the results of Lamm in 5 and 6 and generalized the results of Chang, Wang, Yang 1 , Strzelecki 11 and Wang 13 , 14 to non‐stationary case.     

Light-scattering study of polyelectrolyte complex formation between anionic and cationic nanogels in an aqueous salt-free system

We studied complex formation in an aqueous salt-free system (pH approximately 3 and at 25 degrees C) between nanogel particles having opposite charges. Anionic gel (AG) and cationic gel (CG) particles consist of lightly cross-linked N-isopropylacrylamide (NIPA) copolymers with 2-acrylamido-2-methylpropane sulfonic acid and with 1-vinylimidazole, respectively. The number of charges per particle was -4490 for AG and +20 300 for CG, as estimated from their molar masses (3.33 MD for AG and 11.7 MD for CG) by static light scattering (SLS) and their charge densities (1.35 mmol/g for AG and 1.74 mmol/g for CG) by potentiometric titration. The complexes were formed through the addition of AG to CG and vice versa using a turbidimetric titration technique. At the endpoint of the titration, the aggregate formed was a complex based upon stoichiometric charge neutralization: CG(n)()(+) + xAG(m)()(-) --> CG(n)()(+) (AG(m)()(-))(x)() where x = (n)()/(m)(). At different stages of the titration before the endpoint, the resulting complexes were examined in detail using dynamic light scattering, SLS, and electrophoretic light scattering (ELS). The main results are summarized as follows: (i) When AG with a hydrodynamic radius (R(h)) of 119 nm is added to CG (R(h) approximately 156 nm), the (R(h)) of the complex size decreases from 156 to 80 nm. (ii) In contrast to this (R(h)) change, the molar mass increases from 11.7 MD to 24 MD with increasing amounts of added AG. (iii) Upon addition of CG to AG, the complex formed has the same size ((R(h)) approximately 80 nm) and the same molar mass (55 +/- 2.5 MD) until 55 +/- 5% of AG has been consumed in the complexation. To understand these results, we used the following two models: the random model (RM), in which the added AG particles uniformly bind to all of the CG particles in the system via a strong electrostatic attraction, and the all-or-none model (AONM), in which part of the AG particles in the system preferably bind to the added CG particles to neutralize their electric charges but the other AG particles are uncomplexed and remain in the system. The complex formations upon addition of AG to CG and CG to AG were elucidated in terms of RM and AONM, respectively.     

Structure based studies of the adaptive diversification process of congerins

Summary The isoforms of a fish galectin, congerins I and II, have several features that make them suitable for a study of accelerated process of molecular diversification based on 3D structures: They have been generated by a gene duplication, and still maintain 47% amino acid sequence identity to each other. Their genes show very high K A/K S ratio, and are though to be components of fish defense system. The crystal systems for a high-resolution analysis are known for both proteins. A series of works with biochemistry, molecular biology, and X-ray crystallography techniques have suggested that the two proteins might have evolved under differential selection pressures. Congerin I appeared to be a stabilized version of galectin-1. Congerin II was shown to be adapted to a new carbohydrate-ligand. The 3D structures of the wild type and mutant proteins have revealed the probable cause and consequence of the selection pressure responsible for the diversification of congerins.     

Polymer microarrays for cellular adhesion

Microarray screening of polymer libraries for cellular adhesion was developed utilising a thin film of agarose to allow unsurpassed localisation of cell binding onto the array substrate and the discovery of cell specific polymers.