Midkine as a factor to counteract the deposition of amyloid β-peptide plaques: in vitro analysis and examination in knockout mice

<p>Abstract</p> <p>Background</p> <p>Midkine is a heparin-binding cytokine involved in cell survival and various inflammatory processes. Midkine accumulates in senile plaques of patients with Alzheimer's disease, while it counteracts the cytotoxic effects of amyloid β-peptide and inhibits its oligomerization. The present study was conducted to understand the role of midkine upon plaque formation of amyloid β-peptide.</p> <p>Methods</p> <p>A surface plasmon assay was performed to determine the affinity of midkine for amyloid β-peptide. The deposition of amyloid β-peptide was compared in the brain of wild-type and midkine-deficient mice. An effect of midkine to microglias was examined by cell migration assay.</p> <p>Results</p> <p>Midkine bound to amyloid β-peptide with the affinity of 160 nM. The C-terminal half bound to the peptide more strongly than the N-terminal half, and heparin inhibited midkine from binding to the peptide. Pleiotrophin, which has about 50% sequence identity with midkine also bound to amyloid β-peptide. The deposition of amyloid β-peptide plaques in the cortex and hippocampus was more intense in 15-month-old midkine-deficient mice, compared to the corresponding wild-type mice. Midkine promoted migration of microglias in culture.</p> <p>Conclusions</p> <p>These results are consistent with the view that midkine attenuates the deposition of amyloid β-peptide plaques, and thus progression of Alzheimer's disease, by direct binding and also by promoting migration of microglias.</p

Absorption and Cleavage Spinach Carotenoids in Inverted Quail Intestine and Transfer of the Carotenoids into Egg Yolk

At incubation with spinach carotenoid of inverted quail intestine,β-carotene was quickly absorbed into the intestinal mucosa and then changed to retinol,passing out of the mucosa.The majority of the xanthophyll including lutein,after absorption into the mucosa,passed out of the mucosa in intact form,and the velocities varied per xanthophylls in descending order of lutein,antheraxanthin,and violaxanthin.It became apparent that out of the absorbed xanthophylls,chiefly lutein was incorporated into quail serum LDL,where it was transported into the egg yolk and accumulated.ホウレンソウ葉カロテノイドをウズラ反転小腸とインキュベートするとβ-カロテンは素早く吸収されてレチノールに変化し、粘膜外に移行する。ルテインをはじめとするキサントフィルは小腸に吸収された後β-カロテン開裂酵素の作用をあまり受けずに粘膜を通過するがその吸収と移行の速度はキサントフィルの種類によって大きく異なり、ルテイン、アンセラキサンチン、ビオラキサンチンの順である。さらに、吸収されたキサントフィルのうちに主にルテインは血清LDLに取り込まれて卵黄に移行蓄積されることを明らかにした

Emergency power supply using flywheel and doubly fed induction generator

An emergency power supply (EPS) using an induction generator with a fly-wheel energy storage is investigated. Two different exciting system for the wounded rotor winding have been investigated. The principles of the operation and experimental results are shown. The results of start-up and steady state condition indicate that the inverter rating of the doubly fed induction generator is reduced fairly.INTELEC 2009 - 2009 International Telecommunications Energy Conference : Incheon, South Korea, 2009.10.18-2009.10.2

Multifrequency VLBI Observations of the Broad Absorption Line Quasar J1020+4320: Recently Restarted Jet Activity?

This paper reports very-long-baseline interferometry observations of the radio-loud broad absorption line (BAL) quasar J1020+4320 at 1.7, 2.3, 6.7, and 8.4 GHz using the Japanese VLBI network (JVN) and European VLBI network (EVN). The radio morphology is compact with a size of ~10 pc. The convex radio spectrum is stable over the last decade; an observed peak frequency of 3.2 GHz is equivalent to 9.5 GHz in the rest frame, suggesting an age of the order of ~100 years as a radio source, according to an observed correlation between linear size and peak frequency of compact steep spectrum (CSS) and giga-hertz peaked spectrum (GPS) radio sources. A low-frequency radio excess suggests relic of past jet activity. J1020+4320 may be one of the quasars with recurrent and short-lived jet activity during a BAL-outflowing phase.Comment: 7 pages, 2 figures, 2 tables, accepted for publication in PAS

Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver

Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury. The aim of the current study was to determine the precise mechanism leading to hepatocyte apoptosis after steatotic liver ischemia/reperfusion. Using a murine model of partial hepatic ischemia for 90 min, we examined the levels and pathway of apoptosis, and the peroxynitrite expression, serum alanine aminotransferase levels, and liver histology 1 and 4 h after reperfusion. In the steatotic liver, the peroxynitrite expression increased after ischemia/reperfusion. Significant hepatocyte apoptosis in the steatotic liver was seen after reperfusion, caused by upregulation of cleaved caspases 9 and 3, but not caspase 8. Serum alanine aminotransferase levels were elevated and histological examination revealed severe liver injury in the steatotic liver 4 h after reperfusion. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline. Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine. Our data suggested that the steatotic liver is vulnerable to hepatic ischemia/reperfusion, leading to significant hepatocyte apoptosis by the mitochondrial permeability transition, and thereby resulting in organ dysfunction

Exopolysaccharides From Streptococcus thermophilus ST538 Modulate the Antiviral Innate Immune Response in Porcine Intestinal Epitheliocytes

It was reported that exopolysaccharides (EPSs) from lactobacilli are able to differentially modulate mucosal antiviral immunity. Although research has described the ability of EPSs derived from Streptococcus thermophilus to modulate the mucosal immune system, their impact on antiviral immunity was less explored. In this work, we investigated the capacity of the EPS-producing S. thermophilus ST538 to modulate the innate antiviral immune response triggered by the activation of the Toll-like receptor 3 (TLR3) in porcine intestinal epitheliocytes (PIE cells). Moreover, in order to study the immunomodulatory potential of S. thermophilus ST538 EPS, we successfully developed two mutant strains through the knockout of the epsB or epsC genes. High-performance liquid chromatography and scanning electron microscopy studies demonstrated that the wild type (WT) strain produced as high as 595 μg/ml of EPS in the skim milk medium, while none of the mutant strains (S. thermophilus ΔepsB and ΔepsC) were able to produce EPS. Studies in PIE cells demonstrated that the EPS of S. thermophilus ST538 is able to significantly improve the expression of interferon β (IFN-β), interleukin 6 (IL-6), and C-X-C motif chemokine 10 (CXCL10) in response to TLR3 stimulation. The role of EPS in the modulation of antiviral immune response in PIE cells was confirmed by comparative studies of cell free culture supernatants and fermented skim milks obtained from S. thermophilus ΔepsB and ΔepsC. These results suggest that S. thermophilus ST538 could be used as an immunobiotic strain for the development of new immunologically functional foods, which might contribute to improve resistance against viral infections.Fil: Mizuno, Akira. Tohoku University; JapónFil: Tomotsune, Kae. Tohoku University; JapónFil: Islam, Md Aminul. Tohoku University; JapónFil: Funabashi, Ryutaro. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; Japón. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; ArgentinaFil: Ikeda Ohtsubo, Wakako. Tohoku University; JapónFil: Aso, Hisashi. Tohoku University; JapónFil: Takahashi, Hideki. Tohoku University; JapónFil: Kimura, Katsunori. Meiji Co.; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Sasaki, Yasuko. Meiji University; JapónFil: Kitazawa, Haruki. Tohoku University; Japó

Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan

Comparison of the current study with other sorafenib-interferon combination studies and with single-agent sorafenib studies [25]. (XLSX 12 kb