Multifaceted Analysis of IL-23A- and/or EBI3-Including Cytokines Produced by Psoriatic Keratinocytes

Interleukin (IL) 23 (p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-α, IL-17A, and interferon (IFN)-γ, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer.     

Bubble wake visualization by using photochromic dye

Wake structure of a single “clean bubble”, rising in rectilinear, zigzagging or spiraling path, is experimentally investigated. A single nitrogen gas bubble was produced in a silicone oil pool and the wake structure development in the rear of the rising bubble was visualized by using photochromic dye. The flexibility of this visualization method enabled us to distinguish wake from drift easily. Both bubble motion and wake structure were recorded by using stereo high-speed video camera simultaneously. We present the first experimental support for the existence of the standing eddy at the rear of the clean bubble, as predicted by a previous numerical study by Ryskin and Leal [1984. Journal of Fluid Mechanics 148, 19-35], Dandy and Leal [1986. Physics of Fluids 29(5), 1360-1366] and Blanco and Magnaudet [1995. Physics of Fluids 7(6), 1265-1274]. We study motion of a pair of vortex filaments, which is called double-threaded type wake, in the case of bubble rising in an axi-asymmetric path. Visualization results of multiple formations of horse-shoe type vortices in one period of zigzag motion of rising bubble with shape oscillations, which has not been observed in previous studies are also presented.     

First data from the EGLE experiment onboard the ISS

EGLE is a wide frequency band search- coil magnetometer designed and built at the Roma Tre University. It has been installed onboard the ISS by the Italian astronaut Roberto Vittori on April 25, 2005 within the LAZIO- EGLE experiment carried out during the ENEIDE Soyuz mission. The scope of the experiment is to test EGLE in space and to investigate geomagnetic field variations. The main applications of EGLE are the study of electromagnetic environment inside the ISS, the correlation of magnetic field data with particle fluxes detected by LAZIO particle detector, and the monitoring of ionospheric perturbations possibly caused by Earth seismic activity. Since continuous electromagnetic field measurements on board the ISS are important for diverse space applications, a magnetometer with a suitable design is requested. Appropriate solutions for these applications, which have been adopted by EGLE, are in particular the use of 1- Wire technology and the possibility to detect by means of a search- coil magnetometer a large portion of the ULF frequency band, usually measured by flux- gate probes. To investigate the topside ionosphere electromagnetic environment and stability of Van Allen radiation belts in relation with seismic and anthropogenic electromagnetic emissions, a specific satellite mission (the ESPERIA project) has been designed for the Italian Space Agency (ASI), and up to now a few instruments of its payload have been built and tested in space. One of them is exactly the EGLE search- coil magnetometer. The first magnetic observations performed by this instrument reveal to be promising and demand for a further and deeper analysis based on a longer time series of data.     

Biodegradable β-tricalcium phosphate cement with anti-washout property based on chelate-setting mechanism of inositol phosphate

Novel biodegradable β-tricalcium phosphate (β-TCP) cements with anti-washout properties were created on the basis of chelate-setting mechanism of inositol phosphate (IP6) using β-TCP powders. The β-TCP powders were ball-milled using ZrO₂ beads for 0–6 h in the IP6 solutions with concentrations from 0 to 10,000 ppm. The chelate-setting β-TCP cement with anti-washout property was successfully fabricated by mixing the β-TCP powder ball-milled in 3,000 ppm IP6 solution for 3 h and 2.5 mass% Na₂HPO₄ solution, and compressive strength of the cement was 13.4 ± 0.8 MPa. An in vivo study revealed that the above cement was directly in contact with host and newly formed bones without fibrous tissue layers, and was resorbed by osteoclast-like cells on the surface of the cement. The chelate-setting β-TCP cement with anti-washout property is promising for application as a novel injectable artificial bone with both biodegradability and osteoconductivity.     

Acoustic Emission from a Porcelain Body during Cooling

Quartz grains in porcelain bodies cause cracking. Under the present conditions, acoustic emission (AE) has shown that the cracking occurred in a temperature range of 900°–800°C during cooling from firing at a temperature of 1200°C. This cracking can be explained by a large thermal expansion mismatch that was due to the negative thermal expansion of quartz at temperatures >1000°C and no stress relaxation of the glass phase. At a temperature of 573°C, which is the transition temperature of quartz, AE was not detected by the measuring system that was used, although there were many peripheral cracks around the large quartz grains. The energy release rate of the peripheral cracks at a temperature of 573°C was too low to be detected by the equipment that was used.     

Time trends in sources and dechlorination pathways of dioxins in agrochemically contaminated sediments

Although polychlorinated dibenzo-p-dioxins and dibezofurans (PCDD/Fs) are considered recalcitrant toward biotic and abiotic degradation processes, laboratory studies indicated lateral dechlorination pathways (removal of 2,3,7,8-substituted chlorines) as possible natural remediation strategies under highly reducing conditions prevailing in contaminated sediments. Previous principal component analysis (PCA) of PCDD/Fs in Japanese sediments left unidentified a factor characterized by penta- to octa- homologues fully chlorinated at 1,2,6,9-positions (1,2,6,9-pattern). In the present study, we reexamined PCDD/Fs in sediment cores from urban (Tokyo Bay) and remote (Lake Shinji) areas of Japan using positive matrix factorization (PMF) and revealed a lateral dechlorination fingerprint exhibiting the 1,2,6,9-pattern. Relative molar concentrations of putative lateral dechlorination products linearly increased with sediment depth, suggesting that decades of reaction resulted in the accumulation of hepta- and hexa- chlorinated lateral dechlorination products in the bottom sediment layers. Times required for in situ formation of dechlorination products were estimated to be at least 27.8 +/- 17.9 year(mole %)(-1) in Lake Shinji and 4.7 +/- 0.5 year(mole %)(-1) in Tokyo Bay (both for the formation of 1,2,3,4,6,7,9-HpCDD) and are significantly longer than the dechlorination pathways observed in the laboratory.     

Saccharomyces cerevisiae protein phosphatase Ppz1 and protein kinases Sat4 and Hal5 are involved in the control of subcellular localization of Gln3 by likely regulating its phosphorylation state

A Saccharomyces cerevisiae mutant lacking PPZ1, encoding a serine/threonine protein phosphatase (PPase), is caffeine-sensitive. To clarify the function of Ppz1 in resistance to caffeine, we attempted systematically to identify protein kinase (PKase) whose disruption lead to suppression of caffeine sensitive phenotype of the ?ppz1 disruptant since disruption of PPZ1 might cause caffeine sensitivity by increasing its phosphorylated substrates and we presumed that disruption of genes for PKase sharing the substrate with Ppz1 could restore the resistance through bypassing necessity for dephosphorylation of substrates. Among the 102 viable pkase disruptions, disruption of either SAT4 or HAL5 suppressed the caffeine sensitivity phenotype and increased expression of ENA1, encoding a P-type ATPase of the ?ppz1 disruptant. Because increased expression of ENA1 in the ?ppz1 disruptant was found to be suppressed by disruption of GLN3, localization and phosphorylation of Gln3 in the ?ppz1 disruptant was compared to that in the ?ppz1?sat4 and ?ppz1?hal5 double disruptants. Gln3 was found to accumulate in the nucleus in the ?ppz1 disruptant, and this nuclear localization was abolished by disruption of either SAT4 or HAL5. Interestingly, the level of Gln3 phosphorylation in the ?ppz1?sat4 and ?ppz1?hal5 disruptants decreased relative to wild type independent of caffeine. From these observations, we conclude that Ppz1 controls Gln3 localization by regulating its phosphorylation state in combination with Sat4 and Hal5.     

Aqueous oxidation of substituted dihydroxybenzenes by substituted benzoquinones

Strict anaerobic techniques, HPLC, and spectrophotometry are employed to explore rates of reaction between a series of substituted benzoquinone oxidants and substituted dihydroxybenzene reductants, which represent important redox-active moieties within natural organic matter (NOM). Benzoquinones and dihydroxybenzenes that lack electron-withdrawing substituents exhibit reversible reactions within the acidic range of natural waters. Initial rates for reversible reactions are proportional to [H+]-1, attributable to the greater reactivity of monoprotonated versus diprotonated dihydroxybenzene molecules. Reversible reactions are generally faster for pairs having higher thermodynamic driving force. Concentrations in reversible reactions eventually reach plateau values, which coincide with expected values calculated using standard reduction potentials. If a reactant benzoquinone possesses an electron-withdrawing substituent, reaction progress falls short of expected values. If a product benzoquinone possesses an electron-withdrawing substituent, reaction progress extends beyond what is thermodynamically predicted. Electron-withdrawing substituents raise the susceptibility of benzoquinones to side reactions such as the Michael addition reaction.     

Deciphering cellular functions of protein phosphatases by comparison of gene expression profiles in Saccharomyces cerevisiae

Expression profiles of protein phosphatase (PPase) disruptants were analyzed by use of Pearson's correlation coefficient to find profiles that correlated with those of 316 Reference Gene (RG) disruptants harboring deletions in genes with known functions. Twenty-six Δppase disruptants exhibited either a positive or negative correlation with 94 RG disruptants when the p value for Pearson's correlation coefficient was > 0.2. Some of the predictions that arose from this analysis were tested experimentally and several new Δppase phenotypes were found. Notably, Δsit4 and Δsiw14 disruptants exhibited hygromycin B sensitivity, Δsit4 and Δptc1 disruptants grew slowly on glycerol medium, the Δptc1 disruptant was found to be sensitive to calcofluor white and congo red, while the Δppg1 disruptant was found to be sensitive to congo red. Because on-going analysis of expression profiles of Saccharomyces cerevisiae disruptants is rapidly generating new data, we suggest that the approach used in the present study to explore PPase function is also applicable to other genes.     

Paradigms representing the relationship between the inner of a brain and the outer world

Neuroscience was initially based on simple computer models, and the resulting assumption of blocks of information and step‐by‐step information processing disregards the dynamic features of living neuronal networks. Building semiartificial intelligence in a culture dish using a simple living neuronal network makes comparison with an engineering model easier than when analyzing a complicated brain network. We hypothesize that the status of the neuronal network changes autonomously according to both its own internal state and input from the outer world. Our investigation of such network suggests that an electrical stimulus can make the living neuronal network shift to a particular state, and the response pattern to each input is loosely coupled rather than strictly linked. The critical point we propose regarding brain‐like information processing is that the internal state of the autonomous neuronal network is modified by input from the outer world. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.