Effects of postnatal handling on adult behavior and brain mRNA expression of serotonin receptor, brain-derived neurotrophic factor and GABA-A receptor subunit

Development of brain and behavior is influenced by the interaction of genetic and environmental factors. Postnatal handling, a manipulation that briefly separates mouse offspring from their mother during the postnatal period, has been reported to yield beneficial effects on the behavior of adult offspring. However, brain mechanisms underlying the effects on the behavior have not been well understood. Here we first examined effects of postnatal handling on the behavior of adult male BALB/c mice. Offspring were separated for 15 min every day between postnatal day 1 (P1) and P14 and then various behaviors were tested in the adulthood. Postnatal handling reduced anxiety-like behavior in elevated plus maze and improved spatial learning and memory in Morris water maze without effects on depression-like behavior in forced swim test. Next, to elucidate mechanisms underlying the behavioral effects, we evaluated mRNA expression of the serotonin 1A (5-HT1A) receptor, brain-derived neurotrophic factor (BDNF), and GABA-A receptor subunits in the medial prefrontal cortex, amygdala, dorsal and ventral hippocampi, and dorsal raphe nucleus by quantitative RT-PCR, since these genes and brain regions have been shown to be involved in cognition and emotion. Postnatal handling up-regulated mRNA expression of the 5-HT1A receptor in the dorsal raphe nucleus and down-regulated 5-HT1A receptor mRNA expression in the amygdala on P15 and P71. In adulthood, mRNA expression of BDNF was up-regulated in the amygdala and dorsal hippocampus and down-regulated in the dorsal raphe nucleus, whereas that of GABA-A receptor α2 subunit was down-regulated in the amygdala. Taken together, the present study suggests that postnatal handling reduced anxiety-like behavior and improved learning and memory, which were accompanied by changes in mRNA expression of 5-HT1A receptor, BDNF and GABA-A receptor α2 subunit in the amygdala, 5-HT1A receptor in the dorsal raphe nucleus and BDNF in the dorsal hippocampus

Synthesis of 8β-hydroxy-9(11),13-abietadien-12-one from (+)-dehydroabietylamine and its AhR ligand activity

8β-Hydroxy-9(11), 13-abietadien-12-one (1), an abietane diterpenoid and an aryl hydrocarbon receptor (AhR) ligand, was synthesized in six steps from commercially available (+)-dehydroabietylamine (2). We used the hypervalent iodine catalyst phenyliodine dicarboxylate, a safer alternative to toxic organoselenide reagents, for the oxidative dearomatization of ferruginol (7) to compound 1. Compounds 1 and 2, as well as the synthetic intermediates (compounds 3–7), were evaluated for AhR ligand activity. Only compounds 1 and 7 were active, which suggests that AhR affinity is influenced by the steric environment around the C-18 position of these compounds

Eicosapentaenoic acid conversion by cytochrome P450 BM-3 and its mutants to bio- active epoxide derivatives

Oxidized polyunsaturated fatty acids such as resolvin and protectin are promising functional lipids because they have strong anti-inflammatory effect1). Recently, dietary eicosapentaenoic acid (EPA) was found to exert anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut2). These findings promoted the studies on enzymatic EPA epoxydation to bio-active derivatives. We screened P450 BM-3 and its mutants with rationally modified substrate binding site for conversion of EPA with existence of NADPH regeneration system and ROS decomposing system, catalase. Through the screening, some mutants were found to produce several products (UK1, 2, 3, and 4). Then, these products were purified and identified with LC-MS, NMR, and GC-MS. Finally, these products were identified: UK1 was 14,15:17,18-diepoxy-eicosatrienoic acid (14,15:17,18-DEpETr), UK2 was 17,18-epoxy-eicosatetraenoic acid (17,18-EpETe), UK3 was 14,15-epoxy-eicosatetraenoic acid (14,15-EpETe), UK4 was 11,12-epoxy-eicosatetraenoic acid (11,12-EpETe). The reaction conditions were optimized with P450 BM-3 mutants, and under the optimized conditions, mutant Al4_Ile converted 0.5 mg/ml EPA to 0.20 mg/ml 11,12-EpETe (conversion rate: 38.0% mol/mol). Mutant F87A converted 0.5 mg/ml EPA to 0.19 mg/ml 14,15-EpETe (conversion rate: 36.1% mol/mol). Wild type P450 BM-3 converted 0.5 mg/ml EPA to 0.38 mg/ml 17,18-EpETe (conversion rate: 72.2% mol/mol). Mutant L7V converted 0.5 mg/ml EPA to 0.075 mg/ml 14,15:17,18-DEpETr (conversion rate: 13.5% mol/mol). Please click Additional Files below to see the full abstract

Thermophysical Property Measurements of Refractory Oxide Melts With an Electrostatic Levitation Furnace in the International Space Station

Due to their high melting temperatures and the risk of contamination from the crucibles, molten oxides which melting temperatures are above 2000 °C can hardly be processed using conventional methods. This explains that their thermophysical properties are very scarce. Containerless methods with gas flows have been developed and several thermophysical properties such as density, surface tension, and viscosity have been reported. However, the gas flow has detrimental side effects such as deformation of the sample and induction of internal flows in the molten sample, which affect the accuracy of the measurements. The electrostatic levitation furnace onboard the International Space Station (ISS-ELF), which utilizes the Coulomb force to levitate and melt samples in microgravity, has several advantages for thermophysical property measurements of refractory oxide melts. Levitation without a gas flow coupled to a reduced gravity environment minimizes the required levitation (positioning) force and reduces the deformation as well as the internal flow. This report briefly introduces the ISS-ELF facility and the thermophysical property measurement methods. The measured density, surface tension, and viscosity of molten Al2O3 are then presented and compared with the ones obtained by other methods. Finally, the measured data of refractory oxides whose melting temperatures are above 2,400 °C are summarized

Destruction of mesoscopic chemically modulated domains in single phase high entropy alloy via plastic deformation

Chemically modulated mesoscopic domains in a fcc single phase CrMnFeCoNi equi-atomic high entropy alloy (HEA) are detected by small angle diffraction performed at a synchrotron radiation facility, whereas the mesoscopic domains cannot be detected by conventional X-ray diffraction and 2D mappings of energy dispersive X-ray spectroscopy by scanning electron microscopy and scanning transmission electron microscopy. The mesoscopic domains are deformed and shrieked, and finally destructed by plastic deformation, which is supported by the comprehensive observations/measurements, such as electrical resistivity, Vickers hardness, electron backscattering diffraction, and hard X-ray photoemission spectroscopy. The destruction of the mesoscopic domains causes the decrease in electrical resistivity via plastic deformation, so called K-effect, which is completely opposite to the normal trend of metals. We confirmed that the presence and the size of local chemical ordering or short-range order domains in the single phased HEA, and furthermore, Cr and Mn are related to form the domains

Roles of 5-HT1A receptor in the expression of AMPA receptor and BDNF in developing mouse cortical neurons

The possible interactions between serotonergic and glutamatergic systems during neural development and under the pathogenesis of depression remain unclear. We now investigated roles of 5-HT1A receptor in the mRNA expression of AMPA receptor subunits (GluR1 and GluR2) and brain-derived neurotrophic factor (BDNF) using primary culture of cerebral cortex of mouse embryos. Neurons at embryonic day 18 were cultured for 3 days or 14 days and then treated with 5-HT1A receptor agonist (8-OH-DPAT) for 3 h or 24 h. In neurons cultured for 3 days, 8-OH-DPAT treatment for both 3 h and 24 h increased the mRNA levels of BDNF and GluR1, but not GluR2. In neurons cultured for 14 days, however, 8-OH-DPAT had no effects on these mRNA levels. Next, we examined in vivo roles of 5-HT1A receptor by administration of 8-OH-DPAT to newborn mice. Twenty-four hours after the oral administration of 8-OH-DPAT, the mRNA expression of BDNF was decreased in the frontal cortex, but had no effects on the mRNA expression of GluR1 and GluR2. Taken together, the present study suggests that 5-HT1A receptor activation modulates mRNA expression of AMPA receptor subunit and BDNF in cortical neurons, and the effects are different between in vitro and in vivo

Retraction: NF-κB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65

Article retracte

IOP elevation after STTA

Purpose To evaluate real-world evidence for intraocular pressure (IOP) elevation after subtenon triamcinolone acetonide injection (STTA) in 1252 Japanese patients (1406 eyes) in the Japan Clinical REtina STudy group (J-CREST). Methods This was a multicentre retrospective study of the medical records of 1252 patients (676 men (758 eyes); mean age: 63.8 ± 12.9 years) who received STTA in participating centres between April 2013 and July 2017. Results IOP elevation was observed in 206 eyes (14.7%) and IOP increase ≥ 6 mmHg was found in 328 eyes (23.3%). In total, 106 eyes (7.5%) needed medication and two eyes (0.14%) needed surgical procedures. Younger age, higher baseline IOP, and steroid dose were risk factors associated with IOP elevation. Risk factors associated with IOP increase ≥ 6 mmHg were younger age, lower baseline IOP, steroid dose, and higher incidences of diabetic macular oedema (DME) and uveitis. In contrast, with steroid dose fixed at 20 mg, a lower incidence of DME was a risk factor for increased IOP, suggesting that STTA had dose-dependent effects on IOP increase, especially in patients with DME. Conclusion Our real-world evidence from a large sample of Japanese patients who received STTA showed that the incidence of IOP elevation after STTA was 14.7%, and was associated with younger age, higher baseline IOP, and steroid dose. Thus, IOP should be monitored, especially in patients with younger age, higher baseline IOP, and higher incidences of DME and uveitis

MUC1 in lung adenocarcinoma: cross-sectional genetic and serological study

[Background]Mucin 1 (MUC1) contributes to the growth and metastasis of various cancers, including lung cancer, and MUC1 gene length polymorphisms are associated with susceptibility to lung cancer and its prognosis. In contrast, the association between rs4072037, a single nucleotide polymorphism in MUC1, and lung cancer has not been well studied. [Methods]In the present study, we determined the rs4072037 genotype and measured serum KL-6 levels to evaluate the association between lung adenocarcinoma (ADC) and rs4072037 or serum KL-6 levels. DNA samples were available for 172 patients and these were included in the genomic analyses. In addition, 304 patients were included in the serum analyses. Furthermore, 276 healthy volunteers were included in both genomic and serum analyses. [Results]The rs4072037 genotype was not associated with susceptibility to lung ADC or its prognosis. Interestingly, serum KL-6 levels significantly differed according to rs4072037 genotype in those with T1 or T2 (P < 0.001), N0 or N1 (P = 0.002) and M0 (P < 0.001), but not in those with T3 or T4 (P = 0.882), N2 or N3 (P = 0.616) and M1a or M1b (P = 0.501). Serum KL-6 levels were significantly associated with the presence of lung ADC, as well as with its progression and prognosis, indicating the crucial involvement of KL-6/MUC1 in the development of lung cancer and its progression. [Conclusion]Based on these findings, we conclude that rs4072037 does not have a significant impact on the pathogenesis or prognosis of lung ADC, whereas serum KL-6 levels, which might reflecting the molecular length of MUC1, are significantly associated with lung ADC.This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, collection, analysis and interpretation of data and in writing the manuscript

〈報告〉中上級日本語学習者のための作文ガイドブックの開発

本稿では、中上級学習者のアカデミック・ジャパニーズのための作文学習を支援する作文ガイドブック作成に至る過程を概説し、試作した作文ガイドブックについて報告する。作文学習の際、日本語レベルを超えて共有すべき学習項目を特定し、レベル縦断の内容として各レベルの学習者が必要に応じて参照できれば、より学習効果が上がると考える。そこで、大学の補講日本語コースの中上級作文クラスにおいて、コースシラバス作成、レベルチェック作文分析の結果を踏まえて、作文ガイドブックの作成を行った。複数のレベルで誤用が見られる文体と文脈に関わる文法的な表現の中で学習項目として、文体、引用、接続詞・接続助詞、疑問文、文末表現、「る・た・ている」テンス・アスペクトという６項目を取り上げ、パワーポイント資料を作成した。共有できる学習資源として、作文授業を担当する教師や作文を書く学習者が利用しやすい内容や形式にして公開していくことが重要である。This paper outlines the process leading up to the preparation of a composition guidebook to support intermediate-advanced level learners learning composition for academic Japanese, and reports on the guidebook development. We hypothesize that during the composition learning process, learning will be more effective if learners, regardless of their levels, can refer to a set of essential learning items. Therefore, we prepared a composition guidebook based on the results of course syllabi and level check composition analysis in the intermediate-advanced composition classes of the supplementary Japanese language course of our university. At multiple learner levels, we observed errors related to style and context in grammar expression. Based on the errors, we selected six learning items, namely writing style, quotation, conjunction and conjunctive particles, interrogative sentences, sentence-ending expressions, and tense and aspect. We then created PowerPoint materials. As a learning resource that can be shared, it is important to make it accessible to both the teachers who are in charge of writing composition and to the learners who write compositions, in an easy-to-use content and format