Prolyl Isomerase Pin1 Directly Regulates Calcium/Calmodulin-Dependent Protein Kinase II Activity in Mouse Brains

Calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain and functions as a mediator of calcium signaling. We found that the relative activity of CaMKII was significantly lower in the WT mouse brains than in the Pin1-/- mouse brains. Pin1 binds to phosphorylated CaMKII and weakens its activity. For this reason, the phosphorylation level of tau in the presence of Pin1 is lower than that in the absence of Pin1, and microtubule polymerization is not downregulated by CaMKII when Pin1 is present. These results suggest a novel mechanism of action of Pin1 to prevent neurodegeneration

KH Coder を用いた英語の発音の意識調査に関する研究

　日本人英語学習者にとって英語を話せるようになることは容易ではない。特に大人になってからの言語習得は子どもに比べて、ネイティブスピーカーのような英語を話せるようになるには限界があるとされており、特に発音を習得するのは困難であるとされている。文部科学省(2019）による高校 3 年生を対象とした英語の能力を図るための試験結果からも、日本人英文部語学習者は特に「話すこと」を苦手とする人が多いことがわかっている。本研究では、日本人英語学習者の発音に関する意識を調査するため、アンケート調査によって量的な分析を試みる。研究目的は①「英語の発音に関する苦手、あるいは得意である要因」、②「英語の発音を向上させるのに有効な学習法」、③「どのような英単語に発音上の苦手意識を持つのか」を明らかにすることである。調査は、オンライン上でアンケートを募り、テキスト分析ツールを用いて、自由記述の回答から頻出する単語やコロケーション情報を分析した。研究の結果、①の発音が苦手な要因としては、発音記号自体が読めず、適切な発音方法を知らないのでネイティブスピーカーのように発音できないことなどが挙げられた。得意な要因としては、幼少期に英会話教室などで発音を褒められた経験が自信に繋がっていることなどが挙げられた。②に関しては、ネイティブスピーカーと話すことが最も有効な学習方法であるという回答が多かった。③については、特に日本人英語学習者は l/r の発音の区別が困難であり、英単語は「really」に対して最も苦手意識を抱いていた。全体的な傾向として、大人の日本人英語学習者は英語の発音に関して重要性を高く感じているものの、苦手意識を持つ人の方が多く、英語を学習する時間や機会が足りていないという現状が明らかになった。英語の発音に関しては、教育現場での発音記号の指導などの重要性が改めて感じられた

日本人英語学習者が発音困難な音声要素は何か:音声認識システムを使用したミニマルペアを含む英単語発音実験による検証

日本人英語学習者にとって英語を学習し、習得することは容易ではない。大人の英語学習者は子供に比べネイティブのような発音を習得するのには限界があり、特に思春期以降に発音や言語を学習し習得することは困難であるといえる。今回の研究では日本人英語学習者にとって習得困難な英語の音素は何か、ミニマルペアを含む英単語を用いた発音実験により検証した。実験では母音、子音の中でどの音声要素を発音することが苦手かを調べた。また外来語として日本に入ってきた“coffee”（コーヒー）などの「カタカナ英語」についても発音調査を行った。この結果、日本人英語学習者は、母音、子音、外来語の中では外来語の英単語を最も正確に発音できることが明らかとなった。一方で、母音と子音を比べると、英語の母音を正しく区別して発音する方が子音を区別して発音するよりも難しいことが明らかになった。本実験では、英単語発音の正確性の検証としてスマートフォンの音声認識機能を用いた。これは従来の発音実験で用いられる検証方法とは異なるものであり、本研究は発音実験の方法論の検証という意義もあるものであった

英語音素指導の有効性に関する実験的検証––音声認識システムを使用した発音実験を用いて––

PDF本研究は、日本人英語学習者がスピーキングにおいて、正確な発音をするのが困難な音素を明らかにするために、母音16音素、子音14音素からなる発音実験を実施した。その結果、母音では /əːr/、 /ɔː/、 /oʊ /、 /ʌ/ の4音素が、子音では /f/、 /v/、 /h/、 /n/、 /ŋ/、 /θ/、 /s/、 /z/、 /dz/、 /sí/ の10音素が、日本人英語学習者には正確に発音することが困難であることが明らかになった。これらの発音が難しい音素と、/r/、 /l/ の音素に対して短時間の発音指導を行い、音素によって発音の正確性の改善のしやすさに差があるかを検証したところ、/əːr / の母音音素と、/v/、 /r/、 /dz/、/s/、/h/ の5つの子音音素については、短期間の発音指導によって発音の改善が期待できることが検証された。また、発音指導で扱った3つの発音指導法ごとの効果の差としては、L1Aアプローチの効果が最も高く、続いてIIAアプローチの効果が高く、ALAアプローチの効果が最も低いということが示された。この結果は、日本人英語学習者への発音指導においては、SKT (カタカナ近似音) のようなカタカナ表記の発音の説明が特に有効であることを示唆するものであった。また、本研究では、日本人英語学習者の発音正確性の評価方法として、スマートフォンの音声認識を利用した正確性判断の妥当性についても検証し、その有効性や課題についても明らかにした。departmental bulletin pape

器械運動の授業における動感身体知に関する研究 －前方倒立回転とびを教材として－

This study focused on Front Handspring portion of a gymnastics class, a physical education specialty course within middle-school teacher training. Subjects were students at a women’s junior college. With the aim of establishing training that“ enables one to perform an action after understanding it,” the author proposed a methodological kinetic series based on dynamic sensations. Investigation was then made of dynamic sensations（ kinesthesia） that occurred when performing this series within a class. Conclusions from the results are as follows. 1） Classroom instruction was performed using this kinetic series, and a questionnaire-based survey was made to determine student awareness of the kinds of dynamic sensations generated within the series. 2） Physical learning（ acquisition） of the following is essential to the skillful performance of Front Handspring: Speed of approach（ dynamic hurdle）, the sensations of quick turnover of the ntire body, the sensations of handstand with straight arms, the sensations of repelling the floor through the hands with eye contact, landing with flat feet pressing the floor, and finally getting up with a tight stomach. Within these processes, effective in the acquisition of handstand skills were handstand-capability confirmation （handstands using a wall with open legs and closed legs）, and instructional guidance on“ bridging” these processes. Comparison between the start and end of the classroom session showed a significant change towards a positive direction in the handstand execution abilities of students, and the classroom instruction as performed was shown to be effective. It was also confirmed that dynamic sensations certainly existed within students who participated in the class as performed, that the teaching （classroom instruction） program̶created as based on the dynamic sensations of the instructor and used to engender changes in the dynamic sensations of participating students̶functioned effectively, and further that it had major impact effects

Derivedness index for estimating degree of phenotypic evolution of embryos: a study of comparative transcriptomic analyses of chordates and echinoderms

Species retaining ancestral features, such as species called living fossils, are often regarded as less derived than their sister groups, but such discussions are usually based on qualitative enumeration of conserved traits. This approach creates a major barrier, especially when quantifying the degree of phenotypic evolution or degree of derivedness, since it focuses only on commonly shared traits, and newly acquired or lost traits are often overlooked. To provide a potential solution to this problem, especially for inter-species comparison of gene expression profiles, we propose a new method named "derivedness index" to quantify the degree of derivedness. In contrast to the conservation-based approach, which deals with expressions of commonly shared genes among species being compared, the derivedness index also considers those that were potentially lost or duplicated during evolution. By applying our method, we found that the gene expression profiles of penta-radial phases in echinoderm tended to be more highly derived than those of the bilateral phase. However, our results suggest that echinoderms may not have experienced much larger modifications to their developmental systems than chordates, at least at the transcriptomic level. In vertebrates, we found that the mid-embryonic and organogenesis stages were generally less derived than the earlier or later stages, indicating that the conserved phylotypic period is also less derived. We also found genes that potentially explain less derivedness, such as Hox genes. Finally, we highlight technical concerns that may influence the measured transcriptomic derivedness, such as read depth and library preparation protocols, for further improvement of our method through future studies. We anticipate that this index will serve as a quantitative guide in the search for constrained developmental phases or processes.Published versio

ROS induced Cbl-b expression in rat L6 cells

Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume (Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29: 4798–4811, 2009). However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed that the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2 early-growth response protein (Egr)1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatments such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr1 and/or Egr2 to stimulate Cbl-b expression through the ERK1/2 pathway in L6 myoblasts, since treatment with Egr1/2 siRNA and an ERK1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at −110 to −60 bp of the Cbl-b promoter. Together, this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expression activated by the ERK-Egr signaling pathway

Differences in the Properties and Mirna Expression Profiles between Side Populations from Hepatic Cancer Cells and Normal Liver Cells

AIMS: Because hepatic cancer stem cells (HCSCs) are believed to derive from the conversion of hepatic normal stem cells (HNSCs), the identification of the differences that distinguish HCSCs from HNSCs is important. METHODS: The HCC model was established in F344 rats by DEN induction. Using FACS analysis, side population cells from HCC (SP-HCCs) were isolated from the epithelial-like cells of HCC tissues, and the side population cells from normal liver (SP-NLCs) were isolated from syngeneic normal liver cells. The expression of stem cell markers was detected in both freshly isolated and amplified subpopulations. After induction with HGF, the differentiation of each subpopulation was analyzed by detection of early and late liver markers. In vivo, the biological characteristics of SP-HCCs and SP-NLCs were analyzed by repairing injured livers or forming tumors in nude mice. In addition, the expression of miRNAs was examined in both populations by miRNA array and QRT-PCR. RESULTS: SP-NLCs and SP-HCCs were 4.30±0.011% and 2.100±0.010% of the whole population, respectively. Both SP-NLCs and SP-HCCs displayed greater expression of stem cell markers (CD133 and EpCAM) than NSP-NLCs and NSP-HCCs, respectively (P<0.01), both after fresh isolation and amplification. Upon HGF induction, SP-NLCs generated many ALB positive cells and few CK-7 positive cells, but NSP-NLCs could generate only ALB positive cells. In contrast, SP-HCCs gave rise to only AFP positive cells. As few as 5 × 10⁵ SP-NLCs were capable of repairing liver injury, while the same number of NSP-NLCs could not repair the liver. Furthermore, only 1 × 10⁴ SP-HCCs were necessary to initiate a tumor, while NSP-HCCs could not form a tumor. Compared to SP-NLCs, 68 up-regulated and 10 down-regulated miRNAs were present in SP-HCCs (P<0.01). CONCLUSION: Based on the decisive roles of some miRNAs in the genesis of HCSCs, miRNAs may contribute to the different characteristics that distinguish SP-HCCs from SP-NLCs