Acid-sensing ion channel 3 decreases phosphorylation of extracellular signal-regulated kinases and induces synoviocyte cell death by increasing intracellular calcium.

IntroductionAcid-sensing ion channel 3 (ASIC3) is expressed in synoviocytes, activated by decreases in pH, and reduces inflammation in animal models of inflammatory arthritis. The purpose of the current study was to characterize potential mechanisms underlying the control of inflammation by ASIC3 in fibroblast-like synoviocytes (FLS).MethodsExperiments were performed in cultured FLS from wild-type (WT) and ASIC3-/- mice, ASIC1-/- mice, and people with rheumatoid arthritis. We assessed the effects of acidic pH with and without interleukin-1β on FLS and the role of ASICs in modulating intracellular calcium [Ca(2+)](i), mitogen activated kinase (MAP kinase) expression, and cell death. [Ca(2+)](i) was assessed by fluorescent calcium imaging, MAP kinases were measured by Western Blots; ASIC, cytokine and protease mRNA expression were measured by quantitative PCR and cell death was measured with a LIVE/DEAD assay.ResultsAcidic pH increased [Ca(2+)](i) and decreased p-ERK expression in WT FLS; these effects were significantly smaller in ASIC3-/- FLS and were prevented by blockade of [Ca(2+)]i. Blockade of protein phosphatase 2A (PP2A) prevented the pH-induced decreases in p-ERK. In WT FLS, IL-1β increases ASIC3 mRNA, and when combined with acidic pH enhances [Ca(2+)](i), p-ERK, IL-6 and metalloprotienase mRNA, and cell death. Inhibitors of [Ca(2+)](i) and ERK prevented cell death induced by pH 6.0 in combination with IL-1β in WT FLS.ConclusionsDecreased pH activates ASIC3 resulting in increased [Ca(2+)](i), and decreased p-ERK. Under inflammatory conditions, acidic pH results in enhanced [Ca(2+)](i) and phosphorylation of extracellular signal-regulated kinase that leads to cell death. Thus, activation of ASIC3 on FLS by acidic pH from an inflamed joint could limit synovial proliferation resulting in reduced accumulation of inflammatory mediators and subsequent joint damage

Edge-on galaxies in the HST COSMOS field: the evolution of stellar discs up to z∼\sim0.5

We present a sample of 950 edge-on spiral galaxies found with the use of an artificial neural network in the Hubble Space Telescope COSMOS field. This is currently the largest sample of distant edge-on galaxies. For all galaxies we analyzed the 2D brightness distributions in the F814W filter and measured the radial and vertical exponential scales ($h$ and $h_z$ correspondingly) of the brightness distribution. By comparing the characteristics of distant galaxies with those of nearby objects, we conclude that thin stellar discs with $h/h_z \geq 10$ at $z \approx 0.5$ should be rarer than today. Both exponential scales of the stellar disc show evidence of luminosity-dependent evolution: in faint galaxies the $h$ and $h_z$ values do not change with $z$, in bright (and massive) spiral galaxies both scales, on average, grow towards our epoch.Comment: 5 pages, accepted for publication in MNRAS Letter

Shibusawa Eiichi\u27s View of Japan\u27s Foreign Affairs: Focusing on His Influences on the Meiji Government

From the mid-nineteenth century, Asia, including China and Japan, has been involved in the trend of modernization that was triggered by the activities of European and American powers in this area. In a time of drastic changes, Shibusawa Eiichi (1840-1931) assumed several roles successively: he served as retainer during the bakumatsu period, as official in the Meiji government, and afterwards as businessman, philanthropist, and non-official diplomat. During his service in the Meiji government from 1869 to 1873 and as an entrepreneur from 1873 to 1909, Shibusawa played a key role in devising economic and diplomatic policies for the Meiji government. He is even considered a major designer of modem Japanese economic systems and society. This paper examines Shibusawa Eiichi\u27s view of Japan\u27s foreign affairs and focuses on the way he influenced the Meiji government

The possible evolution of pitch angles of spiral galaxies

The origin and maintenance of spiral structure in galaxies, the correlation between different types of spiral structure and several proposed mechanisms for their generation, and the evolution of spiral arms of galaxies with time are questions that are still controversial. In this note we study the spiral structure in a sample of distant galaxies in order to infer the evolution of spiral arm characteristics with redshift. We considered a sample of 171 face-on spiral galaxies in the Hubble Space Telescope COSMOS (The Cosmic Evolution Survey) field. The galaxies are distributed up to $z \approx 1$ with a mean value of 0.44. For all galaxies, we determined the pitch angles of the spiral arms and analysed their dependence on redshift; a total of 359 arms were measured. Analyses of our measurements combined with the literature data suggest a possible evolution of the pitch angles of spiral galaxies: by the modern epoch the spiral pattern, on average, becomes more tightly wound. This may be a consequence of the general evolution of the structure of galaxies as galaxies become more massive over time and their bulges grow. In addition, the distribution of the cotangent of pitch angle of galaxies indicates the possibility that the dominant mechanism of spiral pattern generation changes over time.Comment: 5 pages, accepted for publication on Astronomy & Astrophysics Letter

Organization of the Expert-Methodological Work, As a Way of Solving Problems in the System of Corporate Governance of Subsidiaries and Dependent Organizations

The article presents the experience of solving the problem of support of the system of corporate governance of subsidiaries and dependent organizations with the necessary information as well as training of specialists for the control system of the group of companies “Delicate moving”. Article is an invitation for discussion and interaction

Structure of amyloid-beta peptides in a complex-with model membranes

Structures of amyloid-beta peptides Aβ1-40. Aβ10-35, β13-23 and Aβ16-22 in a complex with model membranes in solution were obtained on the analysis of NMR experimental data. It has been established that the process of peptide-micelle complex formation occurs through the amino acid residues LI7, F19, F20 and G29-M35