Adrenomedullin in peritoneal effluent expressed by peritoneal mesothelial cells

BACKGROUND: Adrenomedullin (AM) possesses vasodilative and cell-protective properties. Glycine combines with the C-terminal of AM to form mature, physiologically active AM (mAM). AM is reportedly induced by high glucose condition in vascular endothelial or smooth muscle cells; however, little is known on how AM is activated by amidation. To investigate the behavior of AM in patients undergoing peritoneal dialysis (PD), the concentrations of AM, mAM and CA125 were measured. The mAM to AM ratio (mAM/AM ratio) was also evaluated as a marker of amidation activity. METHODS: Twenty patients were recruited for this study. The effluent at the time of the peritoneal equilibration test was collected and AM, mAM and CA125 concentrations were measured. The expression of AM in peritoneal mesothelial cells (PMCs) collected from effluent was also examined with an indirect immunofluorescent method. RESULTS: Mean values of AM and mAM in effluent were 18.1 ± 1.6 and 4.1 ± 0.3 fmol/mL, respectively. In plasma, they were 42.6 ± 3.3 and 5.6 ± 0.6 fmol/mL, respectively. AM concentrations in effluent did not correlate with plasma AM level but correlated well with the dialysate-to-plasma ratio of creatinine (D/P ratio of creatinine). Moreover, in 7 of 20 cases, concentrations of the mAM and mAM/AM ratio in effluent were higher than in plasma. In effluent, AM concentration but not the mAM/AM ratio correlated with CA125 concentration. Immunocytological study revealed diffuse, cytoplasmic expression of AM in PMCs which were collected from effluent during PD. CONCLUSION: AM is expressed by PMCs and actively amidated in the abdominal cavity of patients undergoing PD

Spectroscopy of the spatially-extended Lya emission around a QSO at z=6.4

We have taken a deep, moderate-resolution Keck/Deimos spectra of QSO, CFHQS2329, at z=6.4. At the wavelength of Lya, the spectrum shows a spatially-extended component, which is significantly more extended than a stellar spectrum, and also a continuum part of the spectrum. The restframe line width of the extended component is 21+-7 A, and thus smaller than that of QSO (52+-4 A), where they should be identical if the light is incomplete subtraction of the QSO component. Therefore, these comparisons argue for the detection of a spatially extended Lya nebulae around this QSO. This is the first z>6 QSO that an extended Lya halo has been observed around. Careful subtraction of the central QSO spectrum reveals a lower limit to the Lya luminosity of (1.7+-0.1)x 10^43 erg s^-1. This emission may be from the theoretically predicted infalling gas in the process of forming a primordial galaxy that is ionized by a central QSO. On the other hand, if it is photoionized by the host galaxy, an estimated star-formation rate of >3.0 Msun yr^-1 is required. If we assume the gas is virialized, we obtain dynamical mass estimate of Mdyn=1.2x10^12 Msun. The derived MBH/Mhost is 2.1x10^-4, which is two orders smaller than those from more massive z~6 QSOs, and places this galaxy in accordance with the local M-sigma relation, in contrast to a previous claim on the evolution of M-sigma relation at z~6. We do not claim evolution or non-evolution of the M-sigma relation based on a single object, but our result highlights the importance of investigating fainter QSOs at z~6.Comment: 5 pages, 5 figures. Accepted for publication in MNRAS. A minor computational error fixe

A QSO host galaxy and its Lyalpha emission at z=6.43

We report an optical detection of an extended structure around a QSO at z=6.43 (CFHQSJ2329-0301, the highest redshift QSO currently known) in deep z' and z_r-band images of the Subaru/Suprime-Cam. After a careful PSF (QSO) subtraction, a structure in the z'-band extends more than 4'' on the sky (R_e=11 kpc), and thus, is well-resolved (16sigma detection). The PSF-subtracted z_r-band structure is in a similar shape to that in the z'-band, but less significant with a 3 sigma detection. In the z'-band, a radial profile of the QSO+host shows a clear excess over that of the averaged PSF in 0.8-3'' radius. Since the z'-band includes a Lya emission at z=6.43, the z' flux is perhaps a mixture of the host (continuum light) and its Lya emission, whereas the z_r-band flux is from the host. Through a SED modeling, we estimate 40% of the PSF-subtracted z'-band light is from the host (continuum) and 60% is from Lya emission. The absolute magnitude of the host is M_{1450}=-23.9 (c.f. M_{1450}=-26.4 for the QSO). A lower limit of the SFR(Lya) is 1.6 Msun yr^{-1} with stellar mass ranging 6.2 x 10^8 to 1.1 x 10^10 Msun when 100 Myrs of age is assumed. The detection shows that a luminous QSO is already harbored by a large, star-forming galaxy in the early Universe only after ~840 Myr after the big bang. The host may be a forming giant galaxy, co-evolving with a super massive black hole.Comment: Accepted for publication in MNRAS. A higher resolution pdf is at http://ifa.hawaii.edu/~tomo/QSOhost/QSOhost_v7.pd

ドイツにおける発達障害のある人びとへの社会的支援ードイツ北部現地調査報告

What is a system that allows young people with developmental disabilities to move smoothly from school to employment and how can it be constructed? In order to examine this issue, each country is selected from three regimes based on the welfare regime theory and international comparative research is conducted in the four countries including Japan. This article features Germany as a conservative welfare regime. We report on the results of field survey on institutions and organizations that support youth with developmental disability, mainly conducted in northern Germany, and consider the support of people with developmental disabilities in German welfare state system based on it

A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

The Psmb11-encoded β5t subunit of the thymoproteasome, which is specifically expressed in cortical thymic epithelial cells (cTECs), is essential for the optimal positive selection of functionally competent CD8+ T cells in mice. Here, we report that a human genomic PSMB11 variation, which is detectable at an appreciable allele frequency in human populations, alters the β5t amino acid sequence that affects the processing of catalytically active β5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced β5t expression in cTECs and the homozygotes further exhibited reduction in the cellularity of CD8+ T cells. No severe health problems were noticed in many heterozygous and 5 homozygous human individuals. Long-term analysis of health status, particularly in the homozygotes, is expected to improve our understanding of the role of the thymoproteasome-dependent positive selection of CD8+ T cells in humans

WDR55 Is a Nucleolar Modulator of Ribosomal RNA Synthesis, Cell Cycle Progression, and Teleost Organ Development

The thymus is a vertebrate-specific organ where T lymphocytes are generated. Genetic programs that lead to thymus development are incompletely understood. We previously screened ethylnitrosourea-induced medaka mutants for recessive defects in thymus development. Here we report that one of those mutants is caused by a missense mutation in a gene encoding the previously uncharacterized protein WDR55 carrying the tryptophan-aspartate-repeat motif. We find that WDR55 is a novel nucleolar protein involved in the production of ribosomal RNA (rRNA). Defects in WDR55 cause aberrant accumulation of rRNA intermediates and cell cycle arrest. A mutation in WDR55 in zebrafish also leads to analogous defects in thymus development, whereas WDR55-null mice are lethal before implantation. These results indicate that WDR55 is a nuclear modulator of rRNA synthesis, cell cycle progression, and embryonic organogenesis including teleost thymus development

Chlorophyll a is a favorable substrate for Chlamydomonas Mg-dechelatase encoded by STAY-GREEN

Mg removal from chlorophyll by Mg-dechelatase is the first step of chlorophyll degradation. Recent studies showed that in Arabidopsis, Stay Green (SGR) encodes Mg-dechelatase. Though the Escherichia coli expression system is advantageous for investigating the properties of Mg-dechelatase, Arabidopsis Mg-dechelatase is not successfully expressed in E. coli. Chlamydomonas reinhardtii SGR (CrSGR) has a long, hydrophilic tail, suggesting that active CrSGR can be expressed in E. coli. After the incubation of chlorophyll a with CrSGR expressed in E. coil, pheophytin a accumulated, indicating that active CrSGR was expressed in E. coli. Substrate specificity of CrSGR against chlorophyll b and an intermediate molecule of the chlorophyll b degradation pathway was examined. CrSGR exhibited no activity against chlorophyll b and low activity against 7-hydroxymethyl chlorophyll a, consistent with the fact that chlorophyll b is degraded only after conversion to chlorophyll a. CrSGR exhibited low activity against divinyl chlorophyll a and chlorophyll a', and no activity against chlorophyllide a, protochlorophyll a, chlorophyll c(2), and Znchlorophyll a. These observations indicate that chlorophyll a is the most favorable substrate for CrSGR. When CrSGR was expressed in Arabidopsis cells, the chlorophyll content decreased, further confirming that SGR has Mg-dechelating activity in chloroplasts. (C) 2016 Elsevier Masson SAS. All rights reserved

Mg-dechelation of chlorophyll a by Stay-Green activates chlorophyll b degradation through expressing Non-Yellow Coloring 1 in Arabidopsis thaliana

The first step in chlorophyll a degradation is the extraction of the central Mg. This reaction is catalyzed by Mg-dechelatase encoded by Stay-Green (SGR) in land plants. SGR extracts Mg from chlorophyll a but not from chlorophyll b, and chlorophyll b must be converted to chlorophyll a before degradation. The first reaction of the chlorophyll b to chlorophyll a conversion is catalyzed by chlorophyll b reductase. Non-Yellow Coloring 1 (NYC1) and NYC1 like (NOL) are isozymes of chlorophyll b reductase. When SGR was transiently overexpressed in Arabidopsis, both chlorophyll a and b were degraded, suggesting that the chlorophyll b to chlorophyll a conversion is activated by SGR overexpression. To examine the involvement of chlorophyll b reductases in SGR-induced chlorophyll b degradation, SGR was transiently overexpressed in nyc1, nol, and nyc1 nol double mutants by dexamethasone treatment. It was found that in the wild type and nol mutant, chlorophyll a and b were degraded and all the chlorophyll-binding proteins decreased. Meanwhile, in nyc1 and nyc1 nol mutants, chlorophyll b degradation was suppressed and the light-harvesting complex of photosystem II remained. The mRNA and protein levels of NYC1 increased after SGR overexpression in wild type plants. These results suggest that Mg-dechelation of chlorophyll a by SGR activates chlorophyll b degradation by inducing the expression of NYC1. This is an effective regulation of a metabolic pathway