Hyperosmotic Stress Induces Phosphorylation of CERT and Enhances Its Tethering throughout the Endoplasmic Reticulum

The ceramide transport protein (CERT) delivers ceramide from the endoplasmic reticulum (ER) to the Golgi apparatus, where ceramide is converted to sphingomyelin (SM). The function of CERT is regulated in two distinct phosphorylation-dependent events: multiple phosphorylations in a serine-repeat motif (SRM) and phosphorylation of serine 315 residue (S315). Pharmacological inhibition of SM biosynthesis results in an increase in SRM-dephosphorylated CERT, which serves as an activated form, and an enhanced phosphorylation of S315, which augments the binding of CERT to ER-resident VAMP-associated protein (VAP), inducing the full activation of CERT to operate at the ER–Golgi membrane contact sites (MCSs). However, it remains unclear whether the two phosphorylation-dependent regulatory events always occur coordinately. Here, we describe that hyperosmotic stress induces S315 phosphorylation without affecting the SRM-phosphorylation state. Under hyperosmotic conditions, the binding of CERT with VAP-A is enhanced in an S315 phosphorylation-dependent manner, and this increased binding occurs throughout the ER rather than restrictedly at the ER–Golgi MCSs. Moreover, we found that de novo synthesis of SM with very-long acyl chains preferentially increases via a CERT-independent mechanism under hyperosmotic-stressed cells, providing an insight into a CERT-independent ceramide transport pathway for de novo synthesis of SM.     

Natural Ligand-Mimetic and Nonmimetic Inhibitors of the Ceramide Transport Protein CERT

Lipid transfer proteins (LTPs) are recognized as key players in the inter-organelle trafficking of lipids and are rapidly gaining attention as a novel molecular target for medicinal products. In mammalian cells, ceramide is newly synthesized in the endoplasmic reticulum (ER) and converted to sphingomyelin in the trans-Golgi regions. The ceramide transport protein CERT, a typical LTP, mediates the ER-to-Golgi transport of ceramide at an ER-distal Golgi membrane contact zone. About 20 years ago, a potent inhibitor of CERT, named (1R,3S)-HPA-12, was found by coincidence among ceramide analogs. Since then, various ceramide-resembling compounds have been found to act as CERT inhibitors. Nevertheless, the inevitable issue remains that natural ligand-mimetic compounds might directly bind both to the desired target and to various undesired targets that share the same natural ligand. To resolve this issue, a ceramide-unrelated compound named E16A, or (1S,2R)-HPCB-5, that potently inhibits the function of CERT has recently been developed, employing a series of in silico docking simulations, efficient chemical synthesis, quantitative affinity analysis, protein–ligand co-crystallography, and various in vivo assays. (1R,3S)-HPA-12 and E16A together provide a robust tool to discriminate on-target effects on CERT from off-target effects. This short review article will describe the history of the development of (1R,3S)-HPA-12 and E16A, summarize other CERT inhibitors, and discuss their possible applications.     

Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation

Background: We conducted intratracheal instillations of different molecular weights of polyacrylic acid (PAA) into rats in order to examine what kinds of physicochemical characteristics of acrylic acid-based polymer affect responses in the lung. Methods: F344 rats were intratracheally exposed to a high molecular weight (HMW) of 598 thousand g/mol or a low molecular weight (LMW) of 30.9 thousand g/mol PAA at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months post exposure. Results: HMW PAA caused persistent increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 3 months and 6 months following instillation. On the other hand, LMW PAA caused only transient increases in neutrophil influx, CINC in BALF, and HO-1 in the lung tissue from 3 days to up to 1 week or 1 month following instillation. Histopathological findings of the lungs demonstrated that the extensive inflammation and fibrotic changes caused by the HMW PAA was greater than that in exposure to the LMW PAA during the observation period. Conclusion: HMW PAA induced persistence of lung disorder, suggesting that molecular weight is a physicochemical characteristic of PAA-induced lung disorder.     

Influence of Si species on intergrowth and anisotropic crystal growth of silicalite-1

Silicalite-1 crystals were hydrothermally synthesized from silica gels prepared under different conditions. The influence of the state of Si species in the silica gels and the concentrations of silicate ions and a template agent in the reaction sols on crystal growth of silicalite-1 was examined. The use of silica gels with a high degree of condensation of Si species resulted in the intergrowth of silicalite-1 crystals, whereas a low degree of condensation of Si species led to coffin-shaped crystals. Thus, the degree of condensation of Si species had significant influence on the intergrowth of silicalite-1 crystals. Moreover, at a low silicate concentration, silicalite-1 crystals elongated along the c-axis were obtained. With increasing silicate concentration in the reaction sols, the aspect ratio of silicalite-1 decreased. Furthermore, with decreasing the amount of N(C₃H₇) ₄ ⁺ used as a template agent, the silicalite-1 crystals became larger isotropically. Thus, the growth direction of silicalite-1 crystals was dependent on silicate ion concentration in the reaction sols, but not on N(C₃H₇) ₄ ⁺ concentration.     

Simple Salt‐Coordinated n‐Type Nanocarbon Materials Stable in Air

After more than three decades of molecular and carbon‐based electronics, the creation of air‐ and thermally stable n‐type materials remains a challenge in the development of future p/n junction devices such as solar cells and thermoelectric modules. Here a series of ordinary salts are reported such as sodium chloride (NaCl), sodium hydroxide (NaOH), and potassium hydroxide (KOH) with crown ethers as new doping reagents for converting single‐walled carbon nanotubes to stable n‐type materials. Thermoelectric analyses reveal that these new n‐type single‐walled carbon nanotubes display remarkable air stability even at 100 °C for more than 1 month. Their thermoelectric properties with a dimensionless figure‐of‐merit (ZT) of 0.1 make these new n‐type single‐walled carbon nanotubes a most promising candidate for future n‐type carbon‐based thermoelectric materials.     

Examination of a Thermally Viable Structure for an Unconventional Uni-Leg Mg2Si Thermoelectric Power Generator

We have fabricated an unconventional uni-leg structure thermoelectric generator (TEG) element using quad thermoelectric (TE) chips of Sb-doped n-Mg₂Si, which were prepared by a plasma-activated sintering process. The power curve characteristics, the effect of aging up to 500?h, and the thermal gradients at several points on the module were investigated. The observed maximum output power with the heat source at 975?K and the heat sink at 345?K was 341?mW, from which the ??T for the TE chip was calculated to be about 333?K. In aging testing in air ambient, a remarkable feature of the results was that there was no notable change from the initial resistance of the TEG module for as long as 500?h. The thermal distribution for the fabricated uni-leg TEG element was analyzed by finite-element modeling using ANSYS software. To tune the calculation parameters of ANSYS, such as the thermal conductance properties of the corresponding coupled materials in the module, precise measurements of the temperature at various probe points on the module were made. Then, meticulous verification between the measured temperature values and the results calculated by ANSYS was carried out to optimize the parameters.     

Multi-color light-emitting transistors composed of organic single crystals

We report a novel concept for multi-color light emission from an ambipolar organic single-crystal transistor using natural optical waveguides, the self-absorption effect, Davydov splitting and the unique alignment of the transition dipole moments. We used 9,10-bis-(2,2-diphenylvinyl)-anthracene single crystals to produce blue and green light from identical single-crystal transistors. We also observed red light, which corresponds to the emission from in-gap states that are caused by impurities. Importantly, each of these different colors corresponds to a distinguishable light polarization, which enables us to tune the emission color by using a light polarizer.     

Bipolar DC corona discharge from a floating filamentary metalparticle

The motion of a filamentary particle and also the discharge from a particle have been extensively investigated for the development of a prevention and protection method against breakdown in gas-insulated switchgear. The particle showed several different patterns of motion, e.g., "standing," precession motion, oscillating up and down, etc. Each of these types of motion depends on corona discharge from the particle itself. Since this motion cannot be explained only by monopolar discharge from one end of a particle, bipolar discharge from both ends of a particle occurring simultaneously has been investigated by applying the floating particle method. The particle length and the gap between the particle and electrode were chosen as parameters. From experimental results, several interesting features were obtained. The curve of bipolar corona. current lies between negative and positive corona currents of monopolar curves. There is a sudden current increase at the threshold voltage that seems to be a new feature of the corona current from a filamentary particle. So far, the experimental results indicate that this threshold voltage is not a function of particle length, but it could depend slightly on length. Flashover voltage is a function of particle length and the gap. It decreases with length and increases with the gap