NELF interacts with CBC and participates in 3 \u27 end processing of replication-dependent histone rnRNAs

Negative elongation factor (NELF) is a four subunit transcription elongation factor that has been implicated in numerous diseases ranging from neurological disorders to cancer. Here we show that NELF interacts with the nuclear cap binding complex (CBC), a multifunctional factor that plays important roles in several mRNA processing steps, and the two factors together participate in the 3′ end processing of replication-dependent histone mRNAs, most likely through association with the histone stem-loop binding protein (SLBP). Strikingly, absence of NELF and CBC causes aberrant production of polyadenylated histone mRNAs. Moreover, NELF is physically associated with histone gene loci and forms distinct intranuclear foci that we call NELF bodies, which often overlap with Cajal bodies and cleavage bodies. Our results point to a surprising role of NELF in the 3′ end processing of histone mRNAs and also suggest that NELF is a new factor that coordinates different mRNA processing steps during transcription

A Randomized Phase 2 Trial of Antibiotic Prophylaxis Versus No Intervention for Muscle Biopsy in A Neurology Department

Muscle biopsy can be used to confirm the diagnosis of neuromuscular diseases. However, it is unclear whether antibiotic prophylaxis prior to muscle biopsy is needed to prevent surgical site infection (SSI). We are conducting a phase 2, single-center, open-labeled, prospective randomized trial to clarify the need for antibiotic prophylaxis in patients at low risk for SSI undergoing muscle biopsy. Patients will be randomized to an antibiotic prophylaxis group or a control group, and the incidence of SSI will be compared between the groups. Our findings will clarify the need for antibiotic prophylaxis in this patient population

Importance of physical evaluation using skeletal muscle mass index and body fat percentage to prevent sarcopenia in elderly Japanese diabetes patients

Aims/Introduction To investigate the prevalence of sarcopenia, its related factors and indicators of physical evaluation in elderly diabetes patients. Materials and Methods This was a cross-sectional observation study. A total of 267 diabetes patients (159 men, 108 women) aged >65 years were recruited in the present study. Skeletal muscle mass index, grip strength and usual gait speed were measured to diagnose sarcopenia according to the Asian Working Group for Sarcopenia. Body composition was measured using bioelectrical impedance analysis. Body mass index (BMI) and body fat percentage were evaluated in quartiles to investigate the relationship with sarcopenia. A multiple logistic regression analysis examined sarcopenia-related factors. Results The prevalence of sarcopenia in all participants was 18.7% and increased with age. Sarcopenia decreased as BMI increased (P < 0.01, Cochran-Armitage test). In contrast, the third quartile body fat percentage group showed the lowest prevalence of sarcopenia. A strong positive correlation was observed between body mass and skeletal muscle mass indices (R = 0.702-0.682). Multiple logistic regression analysis showed that sarcopenia was associated with lower BMI, non-use of metformin and lower bone mineral content in men (P < 0.05), and lower bone mineral content, lower serum levels of albumin and older age in women (P < 0.05). Conclusions The present study suggests that diabetes patients with a high body fat percentage in addition to low BMI might develop sarcopenia. It is suggested that physical management in elderly diabetes patients should be carried out based on the evaluation of BMI and body fat percentage to prevent sarcopenia

ERRγ agonist under mechanical stretching manifests hypertrophic cardiomyopathy phenotypes of engineered cardiac tissue through maturation

iPS細胞から成熟した人工心筋組織の作製方法の開発 肥大型心筋症の治療法開発への利用に期待. 京都大学プレスリリース. 2023-10-06.Stretching and stimulating engineered heart tissues to accurately portray hypertrophic cardiomyopathy. 京都大学プレスリリース. 2023-10-17.Engineered cardiac tissue (ECT) using human induced pluripotent stem cell-derived cardiomyocytes is a promising tool for modeling heart disease. However, tissue immaturity makes robust disease modeling difficult. Here, we established a method for modeling hypertrophic cardiomyopathy (HCM) malignant (MYH7 R719Q) and nonmalignant (MYBPC3 G115∗) pathogenic sarcomere gene mutations by accelerating ECT maturation using an ERRγ agonist, T112, and mechanical stretching. ECTs treated with T112 under 10% elongation stimulation exhibited more organized and mature characteristics. Whereas matured ECTs with the MYH7 R719Q mutation showed broad HCM phenotypes, including hypertrophy, hypercontraction, diastolic dysfunction, myofibril misalignment, fibrotic change, and glycolytic activation, matured MYBPC3 G115∗ ECTs displayed limited phenotypes, which were primarily observed only under our new maturation protocol (i.e., hypertrophy). Altogether, ERRγ activation combined with mechanical stimulation enhanced ECT maturation, leading to a more accurate manifestation of HCM phenotypes, including non-cardiomyocyte activation, consistent with clinical observations

Cognitive dysfunction and amyloid β accumulation are ameliorated by the ingestion of green soybean extract in aged mice

AbstractThe effects of soybean extracts were investigated in senescence-accelerated (SAMP10) mice, a mouse model of brain senescence with cognitive dysfunction. Mature soybeans are usually yellow. However, the green soybean retains green color after being ripened. Cognitive functions were significantly better-preserved in aged mice fed green soybean than age-matched control mice with or without yellow soybean feeding. Molecular mechanisms of the beneficial effect of green soybean on brain functions were examined through transcriptome analysis of SAMP10 hippocampus. The high expression of Ptgds was significantly associated with green soybean diet, which encodes lipocalin-type prostaglandin D2 synthase, a putative endogenous amyloid β(Αβ)-chaperone. In consonance, Aplp1 expression was significantly reduced, a member of amyloid precursor proteins. Furthermore, the amount of Aβ 40 and 42 was reduced in the insoluble fraction of cerebral cortex. These results suggest that the intake of green soybean ameliorates cognitive dysfunction of aged mice through the reduction of Aβ accumulation

Evaluation of CNT toxicity by comparison to tattoo ink

ArticleMaterials Today. 14(9): 434-440 (2011)journal articl

Biocompatibility and bone tissue compatibility of alumina ceramics reinforced with carbon nanotubes

信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第906号)・荻原伸英The addition of carbon nanotubes (CNTs) remarkably improves the mechanical characteristics of base materials. CNT/alumina ceramic composites are expected to be highly functional biomaterials useful in a variety of medical fields. Biocompatibility and bone tissue compatibility were studied for the application of CNT/alumina composites as biomaterials. Methods & results: Inflammation reactions in response to the composite were as mild as those of alumina ceramic alone in a subcutaneous implantation study. In bone implantation testing, the composite showed good bone tissue compatibility and connected directly to new bone. An in vitro cell attachment test was performed for osteoblasts, chondrocytes, fibroblasts and smooth muscle cells, and CNT/alumina composite showed cell attachment similar to that of alumina ceramic. Discussion & conclusion: Owing to proven good biocompatibility and bone tissue compatibility, the application of CNT/alumina composites as biomaterials that contact bone, such as prostheses in arthroplasty and devices for bone repair, are expected.ArticleNANOMEDICINE. 7(7):981-993 (2012)journal articl

Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children

BACKGROUND: Restrictive cardiomyopathy in children is rare and outcomes are very poor. However, little information is available concerning genotype-outcome correlations. METHODS: We analyzed the clinical characteristics and genetic testing, including whole exome sequencing, of 28 pediatric restrictive cardiomyopathy patients who were diagnosed from 1998 to 2021 at Osaka University Hospital in Japan. RESULTS: The median age at diagnosis (interquartile range) was 6 (2.25-8.5) years. Eighteen patients received heart transplantations and 5 patients were on the waiting list. One patient died while waiting for transplantation. Pathologic or likely-pathogenic variants were identified in 14 of the 28 (50%) patients, including heterozygous TNNI3 missense variants in 8 patients. TNNT2, MYL2, and FLNC missense variants were also identified. No significant differences in clinical manifestations and hemodynamic parameters between positive and negative pathogenic variants were detected. However, 2- and 5-year survival rates were significantly lower in patients with pathogenic variants (50% and 22%) compared with survival in patients without pathogenic variants (62% and 54%; P=0.0496, log-rank test). No significant differences were detected in the ratio of patients diagnosed at nationwide school heart disease screening program between positive and negative pathogenic variants. Patients diagnosed by school screening showed better transplant-free survival compared with patients diagnosed by heart failure symptoms (P=0.0027 in log-rank test). CONCLUSIONS: In this study, 50% of pediatric restrictive cardiomyopathy patients had pathogenic or likely-pathogenic gene variants, and TNNI3 missense variants were the most frequent. Patients with pathogenic variants showed significantly lower transplant-free survival compared with patients without pathogenic variants.Ishida H., Narita J., Ishii R., et al. Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children. Circulation: Genomic and Precision Medicine 16, 382 (2023); https://doi.org/10.1161/CIRCGEN.122.004054

EMPRESS. XI. SDSS and JWST Search for Local and z~4-5 Extremely Metal-Poor Galaxies (EMPGs): Clustering and Chemical Properties of Local EMPGs

We search for local extremely metal-poor galaxies (EMPGs), selecting photometric candidates by broadband color excess and machine-learning techniques with the SDSS photometric data. After removing stellar contaminants by shallow spectroscopy with Seimei and Nayuta telescopes, we confirm that three candidates are EMPGs with 0.05--0.1 $Z_\odot$ by deep Magellan/MagE spectroscopy for faint {\sc[Oiii]}$\lambda$4363 lines. Using a statistical sample consisting of 105 spectroscopically-confirmed EMPGs taken from our study and the literature, we calculate cross-correlation function (CCF) of the EMPGs and all SDSS galaxies to quantify environments of EMPGs. Comparing another CCF of all SDSS galaxies and comparison SDSS galaxies in the same stellar mass range ($10^{7.0}-10^{8.4} M_\odot$), we find no significant ($>1\sigma$) difference between these two CCFs. We also compare mass-metallicity relations (MZRs) of the EMPGs and those of galaxies at $z\sim$ 0--4 with a steady chemical evolution model and find that the EMPG MZR is comparable with the model prediction on average. These clustering and chemical properties of EMPGs are explained by a scenario of stochastic metal-poor gas accretion on metal-rich galaxies showing metal-poor star formation. Extending the broadband color-excess technique to a high-$z$ EMPG search, we select 17 candidates of $z\sim$ 4--5 EMPGs with the deep ($\simeq30$ mag) near-infrared JWST/NIRCam images obtained by ERO and ERS programs. We find galaxy candidates with negligible {\sc[Oiii]}$\lambda\lambda$4959,5007 emission weaker than the local EMPGs and known high-$z$ galaxies, suggesting that some of these candidates may fall in 0--0.01 $Z_\odot$, which potentially break the lowest metallicity limit known to date