The P2X4 Receptor: Cellular and Molecular Characteristics of a Promising Neuroinflammatory Target

The adenosine 5′-triphosphate-gated P2X4 receptor channel is a promising target in neuroinflammatory disorders, but the ability to effectively target these receptors in models of neuroinflammation has presented a constant challenge. As such, the exact role of P2X4 receptors and their cell signalling mechanisms in human physiology and pathophysiology still requires further elucidation. To this end, research into the molecular mechanisms of P2X4 receptor activation, modulation, and inhibition has continued to gain momentum in an attempt to further describe the role of P2X4 receptors in neuroinflammation and other disease settings. Here we provide an overview of the current understanding of the P2X4 receptor, including its expression and function in cells involved in neuroinflammatory signalling. We discuss the pharmacology of P2X4 receptors and provide an overview of P2X4-targeting molecules, including agonists, positive allosteric modulators, and antagonists. Finally, we discuss the use of P2X4 receptor modulators and antagonists in models of neuroinflammatory cell signalling and disease.     

Sar1 Affects the Localization of Perilipin 2 to Lipid Droplets

Lipid droplets (LDs) are intracellular organelles that are ubiquitous in many types of cells. The LD core consists of triacylglycerols (TGs) surrounded by a phospholipid monolayer and surface proteins such as perilipin 2 (PLIN2). Although TGs accumulate in the phospholipid bilayer of the endoplasmic reticulum (ER) and subsequently nascent LDs buds from ER, the mechanism by which LD proteins are transported to LD particles is not fully understood. Sar1 is a GTPase known as a regulator of coat protein complex Ⅱ (COPⅡ) vesicle budding, and its role in LD formation was investigated in this study. HuH7 human hepatoma cells were infected with adenoviral particles containing genes coding GFP fused with wild-type Sar1 (Sar1 WT) or a GTPase mutant form (Sar1 H79G). When HuH7 cells were treated with oleic acid, Sar1 WT formed a ring-like structure around the LDs. The transient expression of Sar1 did not significantly alter the levels of TG and PLIN2 in the cells. However, the localization of PLIN2 to the LDs decreased in the cells expressing Sar1 H79G. Furthermore, the effects of Sar1 on PLIN2 localization to the LDs were verified by the suppression of endogenous Sar1 using the short hairpin RNA technique. In conclusion, it was found that Sar1 has some roles in the intracellular distribution of PLIN2 to LDs in liver cells.     

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice

Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation.     

Correction and evaluation of the effect due to parasitic motion on primary accelerometer calibration

Primary accelerometer calibration is carried out under the assumption that a vibration exciter gives a rectilinear motion to an accelerometer to be calibrated. However practical vibration given by the vibration exciter includes parasitic motion such as transverse, rocking, and bending motion. Such parasitic motion would give two serious effects on primary calibration results, transverse motion effect and vibration distribution effect. Transverse motion effect is caused by an inner product of the vectors of both transverse motion and transverse sensitivity. On the other hand, the vibration distribution effect is caused by relative motion between a sensing point of accelerometer and a spot sensed by the interferometer. As these effects have close interaction between parasitic motion and measuring instruments, it would be very difficult to evaluate them by measuring independently each component.     

Effects of Sampling Tube Geometry on Soft Clayey Sample Quality Evaluated by Nondestructive Methods

Sample disturbance caused by difference in sampling tube geometry was evaluated by two nondestructive methods: the measurement of the residual effective stress (p_r') by ceramic disc; and the use of the bender element to ascertain the shear wave velocity (V_s), and thus the maximum shear modulus (G_BE). Samples were measured under atmosphere, i.e., not under confined stress conditions. The soil samples were obtained from two sources: reconstituted Kasaoka clay prepared in the laboratory, and at the test site at Takuhoku, Hokkaido, Japan. Samplers with different geometrical designs, referring to the Japanese standard stationary piston sampler, were used for the model ground and field sampling. The geometrical effects of the sampling tube, for example, the thickness of the tube wall, the edge angle, and the existence of a piston were carefully examined. The quality of the samples taken with different samplers was evaluated by p_r' and G_BE, values which were normalized by the in situ vertical effective stress (σ'_vo) and G_f measured by the seismic cone test in the field. It was found from these studies that p_r'/σ'_vo and G_BE/G_f vary considerably due to the geometry of the sampler, with the edge angle of sampling tubes being the most important feature in obtaining high quality samples. The wall thickness, and thus, the area ratio of the sampler is not critical to the sample quality if the edge angle is sharp enough. The existence of the piston does not significantly influence the sample quality in field samples. Furthermore, the correlation between G_BE and p_r' was also investigated, and it was found that the two parameters are strongly dependent.     

GPC Profile Change of Potato Starch with Extrusion Processing

Native potato starch (moisture content 15%) was treated by twin screw extruder under four operating conditions with varying barrel temperatures (110°C–230°C). These modified starch samples were compared to native and drum-dried starch. Starch sample solution for gel chromatography was prepared by the three methods (acidic, alkaline, and neutral methods). They were subjected to gel chromatography on Toyopearl HW-75, and some difference was found among the three gel chromatographic patterns obtained from the same starch solution. This discrepancy among GPC patterns suggests formation of some types of anhydro-bonds between chains of amylopectin and or amylose in the extrusion process. Elevating barrel temperature increases degree of depolymerization. The size of fragments formed with the treatment is bigger than that of oligosaccharides but smaller than that of amylose.     

A Quaternary van der Waals Ferromagnetic Semiconductor AgVP2Se6

The recent realization of 2D magnetism in van der Waals (vdWs) magnets holds promise for future information technology. However, the vdWs semiconducting ferromagnets, which remain rare, are especially important in developing 2D magnetic devices with new functionalities due to the possibility of simultaneous control of the carrier charge and spin. Metal thiophosphate (MTP), a multifunctional vdWs material system that combines the sought‐after properties of complex oxides, is a promising vdWs magnet system. Here, single crystals of a novel vdWs ferromagnetic semiconductor MTP AgVP₂Se₆ with a room‐temperature resistivity of 1 Ω m are successfully synthesized. Due to the nature of vdWs bonding along the c‐axis, the magnetic properties of the few‐layer AgVP₂Se₆ with different thicknesses are characterized on the exfoliated samples. The AgVP₂Se₆ flakes exhibit significant thickness‐dependent magnetic properties, and a rectangular hysteresis loop with a large coercive field of 750 Oe at 2 K and an undiminished Curie temperature of 19 K are observed in the 6.7 nm AgVP₂Se₆ flake. The discovered vdWs ferromagnet AgVP₂Se₆ with semiconducting behavior will provide alternative platforms for exploring 2D magnetism and potential applications in spintronic devices.     

Cathodoluminescence study of AlGaAs/GaAs multilayers grown on ridge-type triangles on GaAs (111)A substrates

We have studied the cathodoluminescence of AlxGa1-xAs/GaAs multilayers grown on ridge-type triangles by molecular beam epitaxy. The compositional variation of Al, as well as the distribution of impurity and/or defect, was revealed by variations in the cathodoluminescence spectra and images. The Al composition in an AlxGa1-xAs layer was highest in the (111)A facet and decreased in the order (100), (411)A, (111)-delta and (110) facets. On the other hand, the carbon concentration was highest in the (411)A facet and decreased in the order (111)A, (111)-delta, (100) and (110) facets. It should be noted that the (111)-delta facet has a significant effect on the redistribution of Al. Although our ridge-type triangles are rather large for the quantum structures, these data have elucidated the self-organization mechanism of the AlxGa1-xAs/GaAs system and have yielded information on the design of quantum structures. We conclude that cathodoluminescence observation is a powerful tool for studying the compositional variation or band structure of three-dimensional microscale or nanoscale construction.     

Enhanced Hole‐Transporting Behavior of Discotic Liquid‐Crystalline Physical Gels

Discotic liquid‐crystalline (LC) physical gels have been prepared by combining the self‐assembled fibers of a low‐molecular‐weight gelator and semiconducting LC triphenylene derivatives. The hole mobilities of the discotic LC physical gels measured by a time‐of‐flight method become higher than those of LC triphenylenes alone. The introduction of the finely dispersed networks of the gelator in the hexagonal columnar phases may affect the molecular dynamics of the liquid crystals, resulting in the enhancement of hole transporting behavior in the LC gel state.