Generation of Stratified Squamous Epithelial Progenitor Cells from Mouse Induced Pluripotent Stem Cells

Background: Application of induced pluripotent stem (iPS) cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, and tailor-made medicine. However, in order to apply iPS cells to mitotic tissue, induction of tissue stem cells that give rise to progeny of the target organ is required. Methodology/Principal Findings: We induced stratified epithelial cells from mouse iPS cells by co-culture with PA6 feeder cells (SDIA-method) with use of BMP4. Clusters of cells positive for the differentiation markers KRT1 or KRT12 were observed in KRT14-positive colonies. We successfully cloned KRT14 and p63 double-positive stratified epithelial progenitor cells from iPS-derived epithelial cells, which formed stratified epithelial sheets consisting of five- to six-polarized epithelial cells in vitro. When these clonal cells were cultured on denuded mouse corneas, a robust stratified epithelial layer was observed with physiological cell polarity including high levels of E-cadherin, p63 and K15 expression in the basal layer and ZO-1 in the superficial layer, recapitulating the apico-basal polarity of the epithelium in vivo. Conclusions/Significance: These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can b

「まじめ」の原型意味論 : 大学生質問紙調査に見られる規範意識

埼玉大学株式会社角産Saitama UniversityKakusan Co., Ltd.原型意味論の立場から「まじめ」が表す意味範疇の原型は「自己基準」「社会基準」を共に満たすような態度であると仮定した。大学生119名を対象に質問紙調査を行い,まず多数の仮想の状況の中で行動する多数の人物について,「まじめ」という形容がどの程度当てはまるか判定させた。その結果,自己基準と社会基準を共に満たす行動パターンの得点が最も高く,自己基準と社会基準のどちらも満たさない行動パターンの得点が最も低かったので,仮説は裏付けられた。また,自己基準だけを満たす行動パターンに比べ社会基準だけを満たす行動パターンの方が得点が高かった。次に回答者自身が「まじめだね/ふまじめだね」と言われた場合,どの程度うれしく感じるか評価させた。概して「まじめ」と言われた場合の方が「ふまじめ」と言われた場合よりも得点が高かったが,それは「どちらとも言えない」にあたる点数を大きく超えてはいなかった。調査全体を通じて「まじめ」に関して大学生が持つ規範意識が観察された。\u27規範的\u27という意味の記述を欠く辞書の改訂が望まれる。The Japanese word majime may mean either \u27earnest\u27 or \u27normative\u27 depending on the context. In a previous paper Yamanaka (1997) argued that these two meanings could be derived from one sememe \u27ready to behave in accordance with an accepted standard, based on a full knowledge of that standard\u27. Based on this, we formulated a prototype for majime, consisting of two elements: the fulfillment of a self standard and that of a social standard. In this paper, we examine actual uses of majime based on a survey of 119 university students. First, hypothetical situations which described acts embodying four combinations of these two elements were presented to subjects, to be judged on the degree to which the character in the situation could be said to be majime. The situations containing and lacking both elements received the highest and lowest scores respectively. Also, the situations only fulfilling a social standard received higher scores than those only fulfilling a self standard. Next, subjects were asked how pleasant they felt if they were told that they were majime/fumajime. On the whole, the responses to majime showed higher scores than the responses to fumajime, but only slightly higher than the score corresponding to the response "I can\u27t say". We conclude not only that the prototype theory of majime is confirmed but also that university students are sensitive to social standards included in the meaning of the word majime, which should be mentioned in its semantic description in dictionaries

Variantes genéticas en el locus 9p21 contribuyen al desarrollo de arteriosclerosis a través de la modulación de ANRIL y CDKN2A/B

Registro creado en correspondencia al grado de doctora de Ada Congrains Castillo.Los estudios de asociación de todo el genoma (GWAS) han identificado variantes genéticas que contribuyen al riesgo de enfermedad cardiovascular (ECV) en el locus del cromosoma 9p21. La región asociada a CVD es adyacente a los dos inhibidores de quinasas dependientes de ciclina (CDKN) 2A y 2B y los últimos exones del ARN no codificante, ANRIL. Todavía no está claro cuál de estas transcripciones o cómo están involucradas en la patogénesis de la aterosclerosis.Genome-wide association studies (GWAS) have identified genetic variants contributing to the risk of cardiovascular disease (CVD) at the chromosome 9p21 locus. The CVD-associated region is adjacent to the two cyclin dependent kinase inhibitors (CDKN)2A and 2B and the last exons of the non-coding RNA, ANRIL. It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis.Japón. Programa de Promoción de Estudios Fundamentales en el Instituto Nacional de Innovación Biomédica de Japón (HR: 22-2-5), el Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología de Japón (KK: 22510211) y la Fundación NOVARTIS para la Investigación Gerontológica (KK).Tesi

タイイク ガクシュウ オ シエン スル ガクシュウ シエン ソフト ノ カイハツ : ヒョウゲン リズム アソビ ドウブツ ランド オ ジレイ トシテ

The aim of this study is to devise an application software for aiding \u27Representative Rhythm Play\u27 in Physical Education and to investigate it\u27s effectiveness. An application software for aiding \u27Representative Rhythm Play\u27 was \u27Animal Land\u27. It consisted of a top menu and a side menu. The top menu consisted of Cover, Explanation for use, Animals in the zoo, Animals in the natural field and Examples for \u27Representative Movement\u27 of animals. The selection of animals was based on how to express the movement quality. The practical experimental lessons of \u27Representative Rhythm Play\u27 consisted of five hours as one unit. Second grade elementary school pupils were used as subjects. In the first lesson, pupils were showed digital teaching materials using computers and projectors and then they were taught how to use them. After they were able to use digital teaching materials using lap top computers by themselves. We let pupils fill in questionnaires after each lesson. The results of the pupil\u27s reaction can be summarized as follows: Almost half of the pupils were interested in digital teaching materials. They accepted the use of computers positively. However, further devise of digital teaching materials is required to allow pupils the use of them more easily concerning effective sound and explanatory words.国立情報学研究所『研究紀要公開支援事業』により電子化

カイゴ ロウジン フクシ シセツ ニュウショ ニ ヨル セイカツ カンキョウ ヘンカ ニ テキオウスル タメノ ヨウイン コウキ コウレイシャ ノ インタビュー チョウサ ヨリ

背景 近年,要介護状態の後期高齢者は急増し,施設利用を自ら選択する意向もみられる.しかし 高齢者にとって施設入所による環境変化は,重大なリスクにつながる.目的 介護老人福祉施設入所による後期高齢者の生活環境変化に適応するための要因を明らかにする.方法 同意が得られた介護老人福祉施設に入所8カ月の94歳の対象Cさんに,インタビュー調査を行った.そして逐語録を作成した後,KJ法の手法を用いて質的に分析した.結果・考察 KJ法の結果66個のラベルが取り出され,ラベルは20個の島に分類された.またこれらの島から11個の表札を抽出した.これらの分析より,生活環境への適応状態には【生活の知恵や判断力に基づいて対処行動がとれる】【自分の居場所が決められる】【職員のケアが適切である】【静かで自然を感じる環境がある】【家族が支えになっている】の5つの要因が関連していることが明らかになった.結論 介護老人福祉施設入所による後期高齢者の生活環境への適応状態を質的に分析した結果, 5つの適応要因の関連が明らかになった.Background As the aging of society progresses rapidly in Japan,the number of elderly with care needs is rising sharply.Yet,living in a facility brings about a change in environment,which can have serious risks for the elderly. Objective The purpose of this study was to reveal the status of adapting to the living environment among the very elderly in special nursing homes.Methods The 94-year-old woman living at a special nursing home for the elderly in Prefecture A for 8 months was interviewed after providing consent to participate.Verbatim transcripts of the interview were made,and the content was qualitatively analyzed using the KJ method.Results/Discussion The total of 66 labels were extracted from the analysis, and the labels were classified into 20 islands.From these islands,11 nameplates were extracted.The analysis revealed that the 94-year-old womanhad adapted to her living environment,and this adaptation was correlated with the following five factors: "can adopt coping behavior based on wisdom regarding living and judgment," "can make decisions about where to live," "care provided is appropriate," "presence of a natural environment in which one can live at peace and quiet," and "family is a source of support." Conclusions We analyzed using the KJ method adaptation to the living environment among the very elderly in special nursing homes.The 94-year-old woman had adapted to her living environment,and this adaptation was correlated with the five factors

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Analysis of amino acid residues involved in cold activity of monomeric isocitrate dehydrogenase from psychrophilic bacteria, Colwellia maris and Colwellia psychrerythraea

Monomeric isocitrate dehydrogenases from psychrophilic bacteria, Colwellia maris and Colwellia psychrerythraea (CmIDH-II and CpIDH-M, respectively) are cold-adapted enzymes and show a high degree of amino acid sequential identity to each other (77%). However, maximum activity of CpIDH-M at optimum temperature is much less than that of CmIDH-II. In the C-terminal region 3 of these enzymes, which was suggested from previous study to be responsible for their distinct catalytic ability, several sequential differences of amino acid residue are present. Among them, ten amino acid residues were exchanged between them by site-directed mutagenesis and several properties of the mutated enzymes were examined in this study. The mutated enzymes of CmIDH-II substituted its Gln671, Leu724 and Phe735 residues with the corresponding residues of CpIDH-M (termed Q671K, L724Q and F735L, respectively) showed lower specific activity and thermostability for activity than the wild-type enzyme. Furthermore, the decreased specific activity was also observed in L693F. In contrast, the corresponding mutants of CpIDH-M, F693L, Q724L and L735F, showed the increased specific activity and thermostability for activity. The catalytic efficiency (K-cat/K-m) values of these mutated CmIDH-II and CpIDH-M were lower and higher than those of their wild-type IDHs, respectively. These results suggest that the Gln671, Leu693, Leu724 and Phe735 residues of CmIDH-II are important for exerting its high catalytic ability. (C) 2013, The Society for Biotechnology, Japan. All rights reserved