Background SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown.ObjectivesOur aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs).ResultsSLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus.ConclusionsThese results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus.

α7 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central nervous system and regarded as potential therapeutic targets for neurodegenerative conditions, such as Alzheimer's disease and schizophrenia. Yet, despite the assumed pathophysiological importance of the α7 nAChR, molecular physiological characterization remains poorly advanced because α7 nAChR cannot be properly folded and sorted to the plasma membranes in most mammalian cell lines, thus preventing the analyses in heterologous expression system. Recently, ER-resident membrane protein NACHO was discovered as a strong chaperone for the functional expression of α7 nAChR in non-permissive cells. Ly6H, a brain-enriched GPI-anchored neurotoxin-like protein, was reported as a novel modulator regulating intracellular trafficking of α7 nAChR. In this study, we established cell lines that stably and robustly express surface α7 nAChR by introducing α7 nAChR, Ric-3, and NACHO cDNA into HEK293 cells (triple α7 nAChR/RIC-3/NACHo cells; TARO cells), and re-evaluated the function of Ly6H. We report here that Ly6H binds with α7 nAChRs on the cell membrane and modulates the channel activity without affecting intracellular trafficking of α7 nAChR. Neuronal nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels composed of combinations of eight α (α2-7, α9, α10) and three β (β2-4) subunits 1,2. Among those, heteromeric α4β2 and homomeric α7 nAChR subtypes are the two major types abundantly expressed in the central nervous system 3. High expression levels of α7 nAChR in the hippocampus, cerebral cortex, and several subcortical limbic regions suggest its contribution to higher brain functions, such as cognition, attention, memory, and sensory-gating 2 , while impaired α7 nAChR signalling has been implicated in cognitive deficits associated with Alzheimer's disease and schizophrenia 1,4,5. In addition, the expression of α7 nAChRs has been detected in various non-neuronal cells, including immune cells, where it plays a role in immunity and inflammation 6,7. Thus, α7 nAChR modulation has emerged as a novel therapeutic strategy for several neurologic and inflammatory disorders 4,5. α7 nAChRs retain several crucial characteristics that make the subtype peculiar, such as faster desensitisation kinetics and higher Ca 2+ permeability compared to other nAChRs 8,9. In addition, α7 nAChRs can be activated by choline, and are blocked by α-bungarotoxin (α-Bgtx) and methyllycaconitine (MLA), whereas α4β2 nAChRs are insensitive to choline, and are not affected by α-Bgtx and MLA 10-12. In addition to fast desensitization kinetics, α7 nAChRs are neither properly oligomerised nor functionally activated in most cell lines, except a few neuronal or neuroendocrine cell lines after transfection with α7 nAChR cDNA 13-16. To overcome these limitations, α7 and glycine chimeric receptor (α7-GlyR) was designed and used to study the ligand-binding domain of α7 nAChR 17,18. It is well known that in most non-permissive cells, the efficiencies in foldi...

The slow nova V2676 Oph was unique in that both C2 and CN molecules were observed during its early phase around the visual brightness maximum. The absorption bands of these molecules were detected using spectroscopic techniques and disappeared within several days. The formation of CO was followed by dust formation, which was confirmed via observations in the latter phase of the nova. The formation of molecules is critically important in understanding the origin of dust grains in novae; however, the formation mechanism of C2 and CN molecules in the early phase of novae remain unclear. Here we report optical spectroscopic observations of the dust-forming nova V2676 Oph in the early phase, and we use these data in addition to spectroscopic observations reported previously to discuss the origin of diatomic molecules in the nova. We conclude that C2 and CN molecules formed in the nova outflow when the outer gas envelope cooled sufficiently and that they survived for more than 2 days but less than 7 days in the nova outflow.

Artificial suppression of radish damping-off disease was induced by repeated soil inoculations with Rhizoctonia solani, binucleate Rhizoctonia (BNR) and Sclerotium rolfsii in pot systems. Soils repeatedly inoculated with R. solani and BNR showed suppressive to disease caused by R. solani and S. rolfsii, while soils repeatedly inoculated with S. rolfsii were suppressive to disease caused by S. rolfsii but not by R. solani. Species of Trichoderma were consistently isolated from soils repeatedly inoculated with R. solani, BNR and S. rolfsii. These Trichoderma spp. accumulated selectively in relation to the fungal species that was repeatedly added to the soils. The ratios of the frequencies of T. viride, T. harzianum and T. hamatum were 5:2:2 and 8:5:2 in soils repeatedly inoculated with R. solani and BNR, respectively. In S. rolfsii-inoculated soils, T. koningii was predominantly isolated. T. viride, T. harzianum and T. hamatum isolates obtained from either R. solani or BNR after repeated additions to the soils suppressed radish damping-off disease caused after challenge inoculations with R. solani or S. rolfsii. Among the Trichoderma species, T. viride consistently yielded high levels of suppression. However, isolates of T. koningii obtained from S. rolfsii-infested soils suppressed disease caused by S. rolfsii but failed to suppress disease caused by R. solani. Generally, the species of Trichoderma accumulated in a selective pattern that was closely related to the species of fungal pathogen used to induce the suppressive soil.

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