Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus

We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H+ ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza

Crucial roles of Robo proteins in midline crossing of cerebellofugal axons and lack of their up-regulation after midline crossing

<p>Abstract</p> <p>Background</p> <p>Robo1, Robo2 and Rig-1 (Robo3), members of the Robo protein family, are candidate receptors for the chemorepellents Slit and are known to play a crucial role in commissural axon guidance in the spinal cord. However, their roles at other axial levels remain unknown. Here we examine expression of Robo proteins by cerebellofugal (CF) commissural axons in the rostral hindbrain and investigate their roles in CF axon pathfinding by analysing Robo knockout mice.</p> <p>Results</p> <p>We analysed the expression of Robo proteins by CF axons originating from deep cerebellar neurons in rodent embryos, focusing on developmental stages of their midline crossing and post-crossing navigation. At the stage of CF axon midline crossing, mRNAs of Robo1 and Robo2 are expressed in the nuclear transitory zone of the cerebellum, where the primordium of the deep cerebellar nuclei are located, supporting the notion that CF axons express Robo1 and Robo2. Indeed, immunohistochemical analysis of CF axons labelled by electroporation to deep cerebellar nuclei neurons indicates that Robo1 protein, and possibly also Robo2 protein, is expressed by CF axons crossing the midline. However, weak or no expression of these proteins is found on the longitudinal portion of CF axons. In <it>Robo1</it>/<it>2 </it>double knockout mice, many CF axons reach the midline but fail to exit it. We find that CF axons express Rig-1 (Robo3) before they reach the midline but not after the longitudinal turn. Consistent with this <it>in vivo </it>observation, axons elicited from a cerebellar explant in co-culture with a floor plate explant express Rig-1. In <it>Rig-1 </it>deficient mouse embryos, CF axons appear to project ipsilaterally without reaching the midline.</p> <p>Conclusion</p> <p>These results indicate that Robo1, Robo2 or both are required for midline exit of CF axons. In contrast, Rig-1 is required for their approach to the midline. However, post-crossing up-regulation of these proteins, which plays an important role in spinal commissural axon guidance, does not appear to be required for the longitudinal navigation of CF axons after midline crossing. Our results illustrate that although common mechanisms operate for midline crossing at different axial levels, significant variation exists in post-crossing navigation.</p

Image-potential band-gap narrowing at a metal/semiconductor interface

GW approximation is used to systematically revisit the image-potential band-gap narrowing at metal/semiconductor interfaces proposed by Inkson in the 1970's. Here we have questioned how the narrowing as calculated from quasi-particle energy spectra for the jellium/Si interface depends on $r_s$ of the jellium. The gap narrowing is found to only weakly depend on $r_s$ (i.e., narrowing $\simeq 0.3$ eV even for a large $r_s = 6)$. Hence we can turn to smaller polarizability in the semiconductor side as an important factor in looking for larger narrowing.Comment: 6 pages, 7 figure

Study on expelled but viable zooxanthellae from giant clams, with an emphasis on their potential as subsequent symbiont sources

Unlike most bivalve shellfishes, giant clams (tridacnines) harbor symbiotic microalgae (zooxanthellae) in their fleshy bodies. Zooxanthellae are not maternally inherited by tridacnine offspring, hence, the larvae must acquire zooxanthellae from external sources, although such algal populations or sources in the environment are currently unknown. It is well known that giant clams expel fecal pellets that contain viable zooxanthellae cells, but whether these cells are infectious or just an expelled overpopulation from the giant clams has not been investigated. In this study, we observed the ultrastructural and photosynthetic competencies of zooxanthellae in the fecal pellets of Tridacna crocea and further tested the ability of these cells to infect T. squamosa juveniles. The ultrastructure of the zooxanthellae cells showed that the cells were intact and had not undergone digestion. Additionally, these zooxanthellae cells showed a maximum quantum yield of photosystem II (Fv/Fm) as high as those retained in the mantle of the giant clam. Under the assumption that feces might provide symbionts to the larvae of other giant clams, fecal pellets from Tridacna squamosa and T. crocea were given to artificially hatched 1-day-old T. squamosa larvae. On the 9th day, 15–34% of the larvae provided with the fecal pellets took up zooxanthellae in their stomach, and on the 14th day, zooxanthellae cells reached the larval margin, indicating the establishment of symbiosis. The rate reaching this stage was highest, ca. 5.3%, in the larvae given whole (nonhomogenized) pellets from T. crocea. The composition of zooxanthellae genera contained in the larvae were similar to those in the fecal pellets, although the abundance ratios were significantly different. This study is the first to demonstrate the potential of giant clam fecal pellets as symbiont vectors to giant clam larvae. These results also demonstrate the possibility that fecal pellets are a source of zooxanthellae in coral reefs.This work was supported by MEXT/JSPS KAKENHI Grant Number 18K19232 to KK

Electronic properties of metal induced gap states at insulator/metal interfaces -- dependence on the alkali halide and the possibility of excitonic mechanism of superconductivity

Motivated from the experimental observation of metal induced gap states (MIGS) at insulator/metal interfaces by Kiguchi {\it et al.} [Phys. Rev. Lett. {\bf 90}, 196803 (2003)], we have theoretically investigated the electronic properties of MIGS at interfaces between various alkali halides and a metal represented by a jellium with the first-principles density functional method. We have found that, on top of the usual evanescent state, MIGS generally have a long tail on halogen sites with a $p_z$-like character, whose penetration depth ($\lambda$) is as large as half the lattice constant of bulk alkali halides. This implies that $\lambda$, while little dependent on the carrier density in the jellium, is dominated by the lattice constant (hence by energy gap) of the alkali halide, where $\lambda_{\rm LiF} < \lambda_{\rm LiCl} < \lambda_{\rm LiI}$. We also propose a possibility of the MIGS working favorably for the exciton-mediated superconductivity.Comment: 7 pages, 9 figure

Gate-induced band ferromagnetism in an organic polymer

We propose that a chain of five-membered rings (polyaminotriazole) should be ferromagnetic with an appropriate doping that is envisaged to be feasible with an FET structure. The ferromagnetism is confirmed by a spin density functional calculation, which also shows that ferromagnetism survives the Peierls instability. We explain the magnetism in terms of Mielke and Tasaki's flat-band ferromagnetism with the Hubbard model. This opens a new possibility of band ferromagnetism in purely organic polymers.Comment: 4 pages, 7 figure

精神疾患におけるマイクログリア由来ニューレグリン発現

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.博士（医学）・乙第1404号・平成29年6月28日Copyright © 2017 Elsevier Inc. All rights reserved