O and Ne K absorption edge structures and interstellar abundance towards Cyg X-2

We have studied the O and Ne absorption features in the X-ray spectrum of Cyg X-2 observed with the Chandra LETG. The O absorption edge is represented by the sum of three absorption-edge components within the limit of the energy resolution and the photon counting statistics. Two of them are due to the atomic O; their energies correspond to two distinct spin states of photo-ionized O atoms. The remaining edge component is considered to represent compound forms of oxide dust grains. Since Cyg X-2 is about 1.4 kpc above the galactic disk, the H column densities can be determined by radio (21 cm and CO emission line) and H alpha observations with relatively small uncertainties. Thus the O abundance relative to H can be determined from the absorption edges. We found that the dust scattering can affect the apparent depth of the edge of the compound forms. We determined the amplitude of the effect, which we consider is the largest possible correction factor. The ratio of column densities of O in atomic to compound forms and the O total abundance were respectively determined to be in the range 1.7^{+3.0}_{-0.9} to 2.8^{+5.1}_{-1.5} (ratio), and 0.63 +/- 0.12 solar to 0.74 +/- 0.14 solar (total), taking into account the uncertainties in the dust-scattering correction and in the ionized H column density. We also determined the Ne abundance from the absorption edge to be 0.75 +/- 0.20 solar. These abundance values are smaller than the widely-used solar values but consistent with the latest estimates of solar abundance.Comment: 20 pages, 3 figures, AASTeX format. Accepted for publication in Ap

Virtual turning points and bifurcation of Stokes curves for higher order ordinary differential equations

For a higher order linear ordinary differential operator P, its Stokes curve bifurcates in general when it hits another turning point of P. This phenomenon is most neatly understandable by taking into account Stokes curves emanating from virtual turning points, together with those from ordinary turning points. This understanding of the bifurcation of a Stokes curve plays an important role in resolving a paradox recently found in the Noumi-Yamada system, a system of linear differential equations associated with the fourth Painleve equation.Comment: 7 pages, 4 figure

Cost-Effectiveness of Administering Rituximab for Steroid-Dependent Nephrotic Syndrome and Frequently Relapsing Nephrotic Syndrome : A Preliminary Study in Japan

With regard to the use of rituximab for patients with steroid-dependent nephrotic syndrome and frequently relapsing nephrotic syndrome, not only has the regimen not been clinically verified but also there is a lack of health economics evidence. Therefore, we conducted a prospective clinical study on 30 patients before (with steroids and immunosuppressants) and after introducing rituximab therapy. Relapse rates and total invoiced medical expenses were selected as the primary endpoints for treatment effectiveness and treatment costs, respectively. As secondary endpoints, cost-effectiveness was compared before and after administering rituximab in relation to previous pharmacotherapy. The observation period was 24 months before and after the initiation of rituximab. We showed that there was a statistically significant improvement in the relapse rate from a mean of 4.30 events before administration to a mean of 0.27 events after administration and that there was a significantly better prognosis in the cumulative avoidance of relapse rate by Kaplan–Meier analysis (p < 0.01). Finally, the total medical costs decreased from 2,923 USD to 1,280 USD per month, and the pre–post cost-effectiveness was confirmed as dominant. We, therefore, conclude that treatment with rituximab was possibly superior to previous pharmacological treatments from a health economics perspective.UTokyo Research掲載「腎臓の難病に対する新しい治療薬の費用対効果」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/cost-effectiveness-of-new-drug-in-treating-incurable-kidney-disease.htmlUTokyo Research "Cost-effectiveness of new drug in treating incurable kidney disease" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/cost-effectiveness-of-new-drug-in-treating-incurable-kidney-disease.htm

Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion

Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion.BackgroundMidkine, a heparin-binding growth factor, is involved in the migration of inflammatory cells. The inflammatory cell migration to the tubulointerstitium of the kidney after ischemia/reperfusion (I/R) injury is attenuated in midkine gene–deficient mice, resulting in better preservation of the tubulointerstitium compared with wild-type mice. In the present investigation, we planned to evaluate the usefulness of antisense midkine for the therapy of ischemic renal failure.MethodsMidkine antisense phosphorothioate oligodeoxyribonucleotide (ODN) at a dose of 1 mg/kg in saline was intravenously administered to mice 1 day before or after I/R. The kidneys were removed for examination 1, 2, 3, and 7 days after I/R.ResultsIt was rapidly incorporated into proximal tubular epithelial cells, and inhibited midkine synthesis, leading to reduced migration of inflammatory cells to the injured epithelial layer. Consequently, the midkine antisense ODN-treated animals exhibited less severe renal damage than untreated or midkine sense ODN-treated animals 2 days after I/R as assessed by morphologic criteria and blood urea nitrogen (BUN) and serum creatinine levels. Midkine expression, BUN, and serum creatinine levels were not significantly different between injection of midkine antisense ODN before and after ischemic injury.ConclusionThese results indicate that intravenous injection of midkine antisense ODN is a candidate for a novel therapeutic strategy against acute tubulointerstitial injury induced by I/R injury

Changes in acetyl-CoA mediate Sik3-induced maturation of chondrocytes in endochondral bone formation

The maturation of chondrocytes is strictly regulated for proper endochondral bone formation. Although recent studies have revealed that intracellular metabolic processes regulate the proliferation and differentiation of cells, little is known about how changes in metabolite levels regulate chondrocyte maturation. To identify the metabolites which regulate chondrocyte maturation, we performed a metabolome analysis on chondrocytes of Sik3 knockout mice, in which chondrocyte maturation is delayed. Among the metabolites, acetyl-CoA was decreased in this model. Immunohistochemical analysis of the Sik3 knockout chondrocytes indicated that the expression levels of phospho-pyruvate dehydrogenase (phospho-Pdh), an inactivated form of Pdh, which is an enzyme that converts pyruvate to acetyl-CoA, and of Pdh kinase 4 (Pdk4), which phosphorylates Pdh, were increased. Inhibition of Pdh by treatment with CPI613 delayed chondrocyte maturation in metatarsal primordial cartilage in organ culture. These results collectively suggest that decreasing the acetyl-CoA level is a cause and not result of the delayed chondrocyte maturation. Sik3 appears to increase the acetyl-CoA level by decreasing the expression level of Pdk4. Blocking ATP synthesis in the TCA cycle by treatment with rotenone also delayed chondrocyte maturation in metatarsal primordial cartilage in organ culture, suggesting the possibility that depriving acetyl-CoA as a substrate for the TCA cycle is responsible for the delayed maturation. Our finding of acetyl-CoA as a regulator of chondrocyte maturation could contribute to understanding the regulatory mechanisms controlling endochondral bone formation by metabolites

Amino Acid Sequence of the α Chain of Chicken AI Hemoglobin I. Amino Acid Sequence of the Tryptic Peptides of the α Chain

Adult chicken hemoglobin is heterogeneous containing two major components, A and AII9). αpolypeptide chain of A I component was purified and subjected to tryptic digestion for 3 hr. Each tryptic peptide was purified by AG 1 x 2 column chromatography, Chromo Beads P column chromatography and paper chromatography in sequence and the amino acid sequence of each peptide was studied. A brief report on the results of this study was already presented as a preliminary communication"\u27. This communication deals with the details on the structural studies of a polypeptide chain of A I component from chicken adult hemoglobin

Changes in acetyl-CoA mediate Sik3-induced maturation of chondrocytes in endochondral bone formation

Kosai A., Horike N., Takei Y., et al. Changes in acetyl-CoA mediate Sik3-induced maturation of chondrocytes in endochondral bone formation. Biochemical and Biophysical Research Communications 516, 1097 (2019); https://doi.org/10.1016/j.bbrc.2019.06.139.The maturation of chondrocytes is strictly regulated for proper endochondral bone formation. Although recent studies have revealed that intracellular metabolic processes regulate the proliferation and differentiation of cells, little is known about how changes in metabolite levels regulate chondrocyte maturation. To identify the metabolites which regulate chondrocyte maturation, we performed a metabolome analysis on chondrocytes of Sik3 knockout mice, in which chondrocyte maturation is delayed. Among the metabolites, acetyl-CoA was decreased in this model. Immunohistochemical analysis of the Sik3 knockout chondrocytes indicated that the expression levels of phospho-pyruvate dehydrogenase (phospho-Pdh), an inactivated form of Pdh, which is an enzyme that converts pyruvate to acetyl-CoA, and of Pdh kinase 4 (Pdk4), which phosphorylates Pdh, were increased. Inhibition of Pdh by treatment with CPI613 delayed chondrocyte maturation in metatarsal primordial cartilage in organ culture. These results collectively suggest that decreasing the acetyl-CoA level is a cause and not result of the delayed chondrocyte maturation. Sik3 appears to increase the acetyl-CoA level by decreasing the expression level of Pdk4. Blocking ATP synthesis in the TCA cycle by treatment with rotenone also delayed chondrocyte maturation in metatarsal primordial cartilage in organ culture, suggesting the possibility that depriving acetyl-CoA as a substrate for the TCA cycle is responsible for the delayed maturation. Our finding of acetyl-CoA as a regulator of chondrocyte maturation could contribute to understanding the regulatory mechanisms controlling endochondral bone formation by metabolites

The Expression of Wnt4 Is Regulated by Estrogen via an Estrogen Receptor Alpha-dependent Pathway in Rat Pituitary Growth Hormone-producing Cells

Wnt signaling is important in many aspects of cell biology and development. In the mouse female reproductive tract, Wnt4, Wnt5a, and Wnt7a show differential expression during the estrus cycle, suggesting that they participate in female reproductive physiology. Although the pituitary is a major gland regulating reproduction, the molecular mechanism of Wnt signaling here is unclear. We elucidated the subcellular distribution of Wnt4 in the pituitary of estrogen-treated ovariectomized female rats. Expression of Wnt4 mRNA increased dramatically, particularly in proestrus compared with estrus and metestrus. Wnt4 protein was observed in the cytoplasm of almost all growth hormone (GH)-producing cells and in only a few thyroid-stimulating hormone β (TSHβ)-producing cells. In rat GH-producing pituitary tumor (MtT/S) cells, estrogen-induced expression of Wnt4 mRNA was completely inhibited by estrogen receptor antagonist ICI 182,780 in vitro. Thus, rat pituitary GH cells synthesize Wnt4 and this is induced by estrogen mediated via an estrogen receptor alpha-dependent pathway