An interpretation on the thermodynamic properties of liquid Pb–Te alloys

The bonding character of liquid lead telluride PbTe\text{PbTe} is thermodynamically investigated in detail. Its possibility as an ionic melt composed of cation Pb2+{\text{Pb}}^{2+} and anion Te2−{\text{Te}}^{2-} is not acceptable, by comparing the ionization energy of Pb\text{Pb} atom, electron affinity of Te\text{Te} atom and the ionic bonding energy due to the cation Pb2+{\text{Pb}}^{2+} and anion Te2−{\text{Te}}^{2-} with the help of structural information. Solid lead telluride PbTe as a narrow band gap semiconductor might yield easily the overlapping of the tail of valence band and that of conduction one. And on melting, it becomes to an ill-conditioned metallic state, which concept is supported by the electrical behaviors of liquid Pb–Te alloys observed by the present authors. As structural information tells us about the partial remain of some sorts of covalent-type mono-dipole and poly-dipole of the molecule PbTe\text{PbTe}, all systems are thermodynamically explained in terms of a mixture of these molecules and cations Pb4+{\text{Pb}}^{4+} and Te2+{\text{Te}}^{2+} and a small amount of the conduction electrons are set free from these elements based on the ternary solution model

Structural evidence of complex formation in liquid Pb–Te alloys

The former analysis of the structural data in liquid Pb–Te alloys, based on the neutron diffraction measurements for this system, was insufficient to obtain the microscopic and spatial configurations in this system. In order to obtain these configurations, we have newly analyzed by using the Reverse Monte Carlo simulations and the method of Voronoi polyhedron. The partial structure factors Sij(Q){S}_{ij}(Q) and thereby gij(r){g}_{ij}(r) are newly estimated by using the former data of neutron diffraction measurements, which are now exactly reproduced by the obtained total structure factors S(Q)S(Q). From these results, it is concluded that the liquid Pb0.5Te0.5 is spatially configured by the mixture of some sorts of covalent-type formation of PbTe molecules and dissociated Pb and/or Te ions with conduction electrons, which result is completely consistent with results of electrical resistivity measurements and also with the thermodynamic analysis

PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo.

In tauopathies, a neural microtubule-associated protein tau (MAPT) is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies

Chemical structure of PE859.

<p>Chemical structure of PE859.</p

Inhibiton of tau aggregation by PE859 was observed using by transmission electron microscopy.

<p>10 μM 3RMBD with no compound (left) and with 0.1 μM PE859 (center) or 1 μM PE859 (right) were incubated at 37°C for 24 h, and stained by 2% phosphotungstic acid. Scale bar = 1 μm.</p

Tail hanging test and rotarod test.

<p>(A) The number of mice showing motor dysfunction in the tail hanging test was shown by survival curve. The rates of motor-dysfunctional mice at the end of the study were 57.1% (28/49) for the vehicle group and 30.6% (15/49) for the PE859 treatment group. The difference between the two groups was significant (p = 0.006; log-rank test). (B) The fall latency of rotarod test. Mean ± SEM, n = 45∼48. The data of dead mice were eliminated because of statistics analysis. The difference between the two groups was significant (p = 0.013; two-way RM ANOVA). *p<0.05, and **p<0.01.</p

Tau constructs used in <i>in vitro</i> assay.

<p>(A) Full length tau. It is the longest tau isoform with 441 amino acids, which includes four microtubule binding domains. (B) 3RMBD tau peptide, lacking N-terminal region, the second microtubule-binding domain (R2), and C-terminal region.</p

The concentration of PE859 in plasma and brain after an oral administration.

<p>The concentration of PE859 in plasma and brain after an oral administration to male ICR mice at 40 mg/kg, were showed by circles with straight line and triangles with dot line, respectively. Mean ± SEM, n = 4.</p

Western blotting and immunohistochemistry.

<p>(A) The amounts of tris buffer-soluble tau (S1), sarkosyl-soluble tau (S2) and sarkosyl-insoluble tau (P2) in the spinal cord. The amount of sarkosyl-soluble tau and sarkosyl-insoluble tau of the PE859 group were significantly smaller than those of the vehicle group (p = 0.009 and 0.008, respectively; Mann-Whitney test). The data were calculated using by the standard curve, which was prepared by the 2-fold serial dilutions of the P2 samples as the pictures of WB (lanes of “Standard”). The lane “V” or “P” of the WB picture means Vehicle or PE859 treated mouse, respectively. Mean ± SEM. a.u., arbitrary unit. **p<0.01. (B) The representative photomicrographs of immunostaining against aggregated tau (AT8) and neuron (NeuN). The spinal cords of the two mice starred in the WB picture of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0117511#pone.0117511.g009" target="_blank">Fig. 9A</a> were used. Scale bar, 0.2 mm.</p

The body weight and mortality rate.

<p>(A) The average body weights of vehicle (squares with straight line) and PE859 treatment group (triangles with dot line) was indicated by mean ± SEM. There was no significant difference between treatment groups (p = 0.71; two-way RM ANOVA). (B) The mortality rate of vehicle (straight line) and PE859 treatment group (dot line) were indicated by survival curve. The rates of dead mice during this study were 8.2% (4/49) for the vehicle group and 2.0% (1/49) for the PE859 treatment group, and there was also no significant difference between the two groups (p = 0.18; log-rank test).</p