Singlet-triplet Crossover in the Two-dimensional Dimer Spin System YbAl3C3

Low-temperature magnetization (M) measurements down to 0.1 K have been performed in magnetic fields up to 14.5 T for a single piece of a tiny single-crystalline sample (0.2 mg weight) of the spin-gap system YbAl3C3. At the base temperature of 0.1 K, several metamagnetic transitions were clearly observed for H // c in the range 6 T < H < 9 T whereas only two transitions were observed, one at 4.8 T and the other at 6.6 T, for H // a. At fields above 9 T, the magnetization becomes almost saturated for both H // a and H // c. The present results indicate that a singlet-triplet crossover occurs in a relatively narrow field range, suggesting a rather weak interdimer interaction in spite of the nearly triangular lattice of Yb ions.Comment: 5 pages, 6 figures, proceedings of ICM 201

Epstein-Barr Virus-Positive Diffuse Large B-cell Lymphoma Arising in Ulcerative Colitis: An Instructive Case Report and Literature Review

Hamamoto Yuichiro, Matsui Saori, Okawa Kiyotaka, et al. Epstein-Barr Virus-Positive Diffuse Large B-cell Lymphoma Arising in Ulcerative Colitis: An Instructive Case Report and Literature Review. Cureus (2024); https://doi.org/10.7759/cureus.72506.Malignant lymphoma is a relatively rare complication in patients with ulcerative colitis (UC) and its etiology is unclear. We present a hard-to-diagnose case of Epstein-Barr virus-positive diffuse large B-cell lymphoma in an elderly patient with UC who was treated with the immunomodulator tacrolimus and herbal medicine including indigo naturalis. Because malignant lymphomas can mimic other inflammatory diseases macroscopically, diagnosis in such cases can be challenging

A Fungal Metabolite Asperparaline A Strongly and Selectively Blocks Insect Nicotinic Acetylcholine Receptors: The First Report on the Mode of Action

Asperparalines produced by Aspergillus japonicus JV-23 induce paralysis in silkworm (Bombyx mori) larvae, but the target underlying insect toxicity remains unknown. In the present study, we have investigated the actions of asperparaline A on ligand-gated ion channels expressed in cultured larval brain neurons of the silkworm using patch-clamp electrophysiology. Bath-application of asperparaline A (10 µM) had no effect on the membrane current, but when delivered for 1 min prior to co-application with 10 µM acetylcholine (ACh), it blocked completely the ACh-induced current that was sensitive to mecamylamine, a nicotinic acetylcholine receptor (nAChR)-selective antaogonist. In contrast, 10 µM asperparaline A was ineffective on the γ-aminobutyric acid- and L-glutamate-induced responses of the Bombyx larval neurons. The fungal alkaloid showed no-use dependency in blocking the ACh-induced response with distinct affinity for the peak and slowly-desensitizing current amplitudes of the response to 10 µM ACh in terms of IC50 values of 20.2 and 39.6 nM, respectively. Asperparaline A (100 nM) reduced the maximum neuron response to ACh with a minimal shift in EC50, suggesting that the alkaloid is non-competitive with ACh. In contrast to showing marked blocking action on the insect nAChRs, it exhibited only a weak blocking action on chicken α3β4, α4β2 and α7 nAChRs expressed in Xenopus laevis oocytes, suggesting a high selectivity for insect over certain vertebrate nAChRs

Microarray analysis of circulating microRNAs in familial Mediterranean fever

Objectives: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in MEFV. Mutations in exon 10 are associated with typical FMF phenotypes, whereas the pathogenic role of variants in exons 2 and 3 remains uncertain. Recent evidence suggests that circulating microRNAs (miRNAs) are potentially useful biomarkers in several diseases. Therefore, their expression was assessed in FMF. Methods: The subjects were 24 patients with FMF who were between attacks: eight with exon 10 mutations (group A), eight with exon 3 mutations (group B), and eight without exon 3 or 10 mutations (group C). We also investigated eight cases of PFAPA as disease controls. Exosome-rich fractionated RNA was subjected to miRNA profiling by microarray. Results: Using the expression patterns of 26 miRNAs, we classified FMF (groups A, B, and C) and PFAPA with 78.1% accuracy. In FMF patients, groups A and B, A and C, and B and C were distinguished with 93.8, 87.5, and 100% accuracy using 24, 30, and 25 miRNA expression patterns, respectively. Conclusions: These findings suggest that expression patterns of circulating miRNAs differ among FMF subgroups based on MEFV mutations between FMF episodes. These patterns may serve as a useful biomarker for detecting subgroups of FMF. © 2017 Japan College of RheumatologyEmbargo Period 12 month

心臓拍動音の精神的安定に対する心理学的・音響学的効果

Aim: We conducted two studies to elucidate the relationship between heartbeat rhythms and relaxation among Japanese babies, young children, and their parents.Subjects and Methods: STUDY 1: Seven parents (age M = 34.3, SD = 5.5 years) with infants or toddlers (age M = 9.4, SD = 6.7 months) participated by listening to three conditions—a heartbeat sound, music, or music with a heartbeat sound—while completing a semantic differential exercise assessing musical imagery. Three types of music (classical, music box, and children’ s songs) were used. Image scores were compared among the three conditions in each type of music. STUDY 2: Participants included 161 parents who listened to three pieces of music, each with a different heartbeat rhythm (patterns A, B, and C). The parents reported their baby or child’ s responses to the music and also self-reported feelings they experienced. Finally, the parents indicated the piece of music they most preferred and related images using the SD exercise. To perform our analyses, we also assessed acoustic characteristics of the three heartbeat sounds.Results: STUDY 1: In the music arranged for a music box, participants evaluated musical imagery as significantly more “airy,” “comfortable,” “feels good,” “relaxing,” “easy,” “awake,” and “amusing” when listening to music with a heartbeat sound, in comparison to the other two conditions (p < .05). STUDY 2: “Rocking the body” and “heard quietly and slept” were the infants’ and toddlers’ responses to the music with a heartbeat sound. Fifty-six parents (34.8%) preferred “pattern A” music, 47 (29.2%) preferred “pattern B,” and 10 (6.3%) preferred “pattern C.” In analysis of “pattern A” acoustics, the mean number of heartbeats per minute, mean heartbeat frequency, maximum heartbeat frequency, and heartbeat Pitch Period Perturbation Quotient (PPQ) were 58/min, 120.3 ± 32.8 Hz, 248.4 Hz, and 11.39%, respectively.Conclusion: This research suggests that a heartbeat sound effective for relaxation has a rhythm of 60 beats/min, low-frequency bandwidth (120–220 Hz), and low percentage of PPQ. Our studies also indicate that music arranged for a music box with a heartbeat sound might be beneficial for inducing relaxation

Genetic legacy of ancient hunter-gatherer Jomon in Japanese populations

Yamamoto K., Namba S., Sonehara K., et al. Genetic legacy of ancient hunter-gatherer Jomon in Japanese populations. Nature Communications 15, 9780 (2024); https://doi.org/10.1038/s41467-024-54052-0.The tripartite ancestral structure is a recently proposed model for the genetic origin of modern Japanese, comprising indigenous Jomon hunter-gatherers and two additional continental ancestors from Northeast Asia and East Asia. To investigate the impact of the tripartite structure on genetic and phenotypic variation today, we conducted biobank-scale analyses by merging Biobank Japan (BBJ; n = 171,287) with ancient Japanese and Eurasian genomes (n = 22). We demonstrate the applicability of the tripartite model to Japanese populations throughout the archipelago, with an extremely strong correlation between Jomon ancestry and genomic variation among individuals. We also find that the genetic legacy of Jomon ancestry underlies an elevated body mass index (BMI). Genome-wide association analysis with rigorous adjustments for geographical and ancestral substructures identifies 132 variants that are informative for predicting individual Jomon ancestry. This prediction model is validated using independent Japanese cohorts (Nagahama cohort, n = 2993; the second cohort of BBJ, n = 72,695). We further confirm the phenotypic association between Jomon ancestry and BMI using East Asian individuals from UK Biobank (n = 2286). Our extensive analysis of ancient and modern genomes, involving over 250,000 participants, provides valuable insights into the genetic legacy of ancient hunter-gatherers in contemporary populations

How Newcomers of Kindergarten Pupils Create Comfort Places and Organize Their Play?: Focusing on the Cases of the Young Children’s "Pretend-play" and "Inquiring Creatures"

本研究は、幼稚園入園児が園生活を過ごす中で、どのように居場所を形成しながら自分の遊びを広げていくのか、その変化の過程と関係を微視的に検討するものである。特に、福井大学教育学部附属幼稚園の新入園3歳児が入園期から園生活で安定・安心を得ていく過程とともに、新入園児が園生活の中で好む「見立て遊び」や「生き物探し」の二点の事例の中で、情緒の安定や遊びへの取り組みを変化させる過程や関係を検討する。本研究はアクションリサーチの手法を用いて3歳児2クラスの40名を対象とする。その中でも、見立て遊びや生き物探しに関わる中で自身の安定・安心を獲得し、遊びを展開していったK男、Y男、T男の3名に着目して、それぞれの変容過程を検討していく。 結果、居場所づくりの過程では、幼児の心理的安全性と自発的挑戦志向性を教師との関係の中で保障することの重要性が示された。特に、幼稚園という場に対する幼児の安心感を意識するだけでなく、遊びに向かう活動の中で幼児にとっての場や対象の位置付けが少しずつ変化していく過程と活動や活動内の対象との向き合い方が変化していく過程を教師は丁寧に捉えていた。これらの点から、幼児の心理的安全性と自発的挑戦志向性を促す素地には、場と遊びの間で生じる幼児の情動や情感交流のあり方が多様に変容することを踏まえて幼児の内面と表出を汲み取ることが新入園期において大切であると考えられる。つまり、新入園期の居場所は固定した場ではなく、常に揺れ動きながら生成変化するものであると考えられる。遊びづくりの過程では、教師は幼児が一人でいる状況、誰かと並行遊びをしている状況、そして協同で取り組もうとしている状況など、各状況に個々の幼児が自発的に取り組む姿勢、活動への意欲、主体的な関わりを重ねながら遊びの深まりを丁寧に見ることが重要である。以上の点を踏まえて、居場所づくりと遊びの組織化に関しては、(1)新入園児の思考が具体的な表象として表出される過程、(2)新入園児の思考と行動の不一致に対する教師の援助過程、(3)新入園児が目標と遂行を意識するための環境設定や援助方略が相互に絡み合いながら、入園期の幼児が園を安定・安心かつ自己発揮できる場所として位置付けるようになっていく過程の見取りが重要であることを明らかにした。departmental bulletin pape

Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis

journal articl

Mild Electrical Stimulation with Heat Shock Ameliorates Insulin Resistance via Enhanced Insulin Signaling

Low-intensity electrical current (or mild electrical stimulation; MES) influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. In addition, it was also previously reported that heat shock protein 72 (Hsp72) alleviates hyperglycemia. Thus, we applied MES in combination with heat shock (HS) to in vitro and in vivo models of insulin resistance. Here we show that 10-min treatment with MES at 5 V (0.1 ms pulse duration) together with HS at 42°C increased the phosphorylation of insulin signaling molecules such as insulin receptor substrate (IRS) and Akt in HepG2 cells maintained in high-glucose medium. MES (12 V)+mild HS treatment of high fat-fed mice also increased the phosphorylation of insulin receptor β subunit (IRβ) and Akt in mice liver. In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a week for 12–15 weeks significantly decreased fasting blood glucose and insulin levels and improved insulin sensitivity. The treated mice showed significantly lower weight of visceral and subcutaneous fat, a markedly improved fatty liver and decreased size of adipocytes. Our findings indicated that the combination of MES and HS alleviated insulin resistance and improved fat metabolism in diabetes mouse models, in part, by enhancing the insulin signaling pathway

Multi -ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.We thank the Director of Health Malaysia for supporting the work described in the South Asian (SAS) population: the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) study. The MyEIRA study was funded by grants from Ministry of Health Malaysia (NMRR-08-820-1975) and the Swedish National Research Council (DNR-348-2009-6468). The GENRA study and the CARDERA genetics cohort genotyping were funded by Versus Arthritis (grant reference 19739 to I.C.S.). The Nurses’ Health Study (NHS cohort) is funded by the National Institutes of Health (NIH) (R01 AR049880, UM1 CA186107, R01 CA49449, U01 CA176726 and R01 CA67262). The Swedish EIRA study was supported by the Swedish Research Council (to L.K., L.P. and L.A.). S.S. was in part supported by the Mochida Memorial Foundation for Medical and Pharmaceutical Research, Kanae Foundation for the Promotion of Medical Science, Astellas Foundation for Research on Metabolic Disorders, JCR Grant for Promoting Basic Rheumatology, and Manabe Scholarship Grant for Allergic and Rheumatic Diseases. I.C.S. is funded by the National Institute for Health and Care Research (NIHR) Advanced Research Fellowship (grant reference NIHR300826). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. K.A.S. is supported by the Sherman Family Chair in Genomic Medicine and by a Canadian Institutes for Health Research Foundation Grant (FDN 148457) and grants from the Ontario Research Fund (RE-09-090) and Canadian Foundation for Innovation (33374). S.-C.B. is supported by the Basic Science Research Program through the NRF funded by the Ministry of Education (NRF-2021R1A6A1A03038899). R.P.K. and J.C.E. are funded by NIH (UL1 TR003096). C.M.L. is partly funded by the NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. T. Arayssi was partially supported by the National Priorities Research Program (grant 4-344-3-105 from the Qatar National Research Fund, a member of Qatar Foundation). M. Kerick and J.M. are funded by Rheumatology Cooperative Research Thematic Network program RD16/0012/0013 from the Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation). Y.O. is funded by JSPS KAKENHI (19H01021 and 20K21834), AMED (JP21km0405211, JP21ek0109413, JP21ek0410075, JP21gm4010006 and JP21km0405217), JST Moonshot R&D (JPMJMS2021 and JPMJMS2024), Takeda Science Foundation, and the Bioinformatics Initiative of Osaka University Graduate School of Medicine. Y. Kochi is funded by grants from Nanken-Kyoten, TMDU and Medical Research Center Initiative for High Depth Omics. S.R. is supported by UH2AR067677, U01HG009379, R01AR063759 and U01HG012009