重症患者における下痢の量と死亡の用量反応関係：過去起点コホート研究

京都大学新制・課程博士博士(医学)甲第24968号医博第5022号新制||医||1069(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 中山 健夫, 教授 佐藤 俊哉, 教授 江木 盛時学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Identification of amino acid residues of mammalian mitochondrial phosphate carrier important for its functional expression in yeast cells, as achieved by PCR-mediated random mutation and gap-repair cloning

The mitochondrial phosphate carrier (PiC) of mammals, but not the yeast one, is synthesized with a presequence. The deletion of this presequence of the mammalian PiC was reported to facilitate the import of the carrier into yeast mitochondria, but the question as to whether or not mammalian PiC could be functionally expressed in yeast mitochondria was not addressed. In the present study, we first examined whether the defective growth on a glycerol plate of yeast cells lacking the yeast PiC gene could be reversed by the introduction of expression vectors of rat PiCs. The introduction of expression vectors encoding full-length rat PiC (rPiC) or rPiC lacking the presequence (ΔNrPiC) was ineffective in restoring growth on the glycerol plates. When we examined the expression levels of individual rPiCs in yeast mitochondria, ΔNrPiC was expressed at a level similar to that of yeast PiC, but that of rPiC was very low. These results indicated that ΔNrPiC expressed in yeast mitochondria is inert. Next, we sought to isolate “revertants” viable on the glycerol plate by expressing randomly mutated ΔNrPiC, and obtained two clones. These clones carried either of two mutations, F267S or F282S; and these mutations restored the transport function of ΔNrPiC in yeast mitochondria. These two Phe residues were conserved in human carrier (hPiC), and the transport function of ΔNhPiC expressed in yeast mitochondria was also markedly improved by their substitutions. Thus, substitution of F267S or F282S was concluded to be important for functional expression of mammalian PiCs in yeast mitochondria

Seasonal variations of the prevalence of metabolic syndrome and its markers using big-data of health check-ups

Seto H., Toki H., Kitora S., et al. Seasonal variations of the prevalence of metabolic syndrome and its markers using big-data of health check-ups. Environmental Health and Preventive Medicine 29, 2 (2024); https://doi.org/10.1265/ehpm.23-00216.Background: It is crucial to understand the seasonal variation of Metabolic Syndrome (MetS) for the detection and management of MetS. Previous studies have demonstrated the seasonal variations in MetS prevalence and its markers, but their methods are not robust. To clarify the concrete seasonal variations in the MetS prevalence and its markers, we utilized a powerful method called Seasonal Trend Decomposition Procedure based on LOESS (STL) and a big dataset of health checkups. Methods: A total of 1,819,214 records of health checkups (759,839 records for men and 1,059,375 records for women) between April 2012 and December 2017 were included in this study. We examined the seasonal variations in the MetS prevalence and its markers using 5 years and 9 months health checkup data and STL analysis. MetS markers consisted of waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG). Results: We found that the MetS prevalence was high in winter and somewhat high in August. Among men, MetS prevalence was 2.64 ± 0.42 (mean ± SD) % higher in the highest month (January) than in the lowest month (June). Among women, MetS prevalence was 0.53 ± 0.24% higher in the highest month (January) than in the lowest month (June). Additionally, SBP, DBP, and HDL-C exhibited simple variations, being higher in winter and lower in summer, while WC, TG, and FPG displayed more complex variations. Conclusions: This finding, complex seasonal variations of MetS prevalence, WC, TG, and FPG, could not be derived from previous studies using just the mean values in spring, summer, autumn and winter or the cosinor analysis. More attention should be paid to factors affecting seasonal variations of central obesity, dyslipidemia and insulin resistance

Association between posterior occlusal support and tooth loss in a population-based cohort: The OHSAKA study

Mameno T., Otsuki N., Wada M., et al. Association between posterior occlusal support and tooth loss in a population-based cohort: The OHSAKA study. Journal of Dentistry 148, 105144 (2024); https://doi.org/10.1016/j.jdent.2024.105144.Objectives: This study aimed to assess the association between posterior occlusal support (POS) and the risk of tooth loss in older adults aged ≥75 years. Methods: This longitudinal study analyzed 94,422 participants who participated in multiple dental check-ups provided as part of the public healthcare services in Osaka, Japan, from 2018 to 2022. The participants were categorized into nine groups (A1–3, B1–4, and C1 and C2) according to their POS status using the Eichner index at baseline. The dental charts were compared between the initial and final assessments to assess tooth loss. Logistic regression analysis was used to examine the association between POS status and tooth loss, adjusted for several covariates, including age, sex, body mass index, periodontal status, oral hygiene, history of diabetes, history of hypertension, attendance at the annual dental check-up, and observational period. Furthermore, stratified logistic regression analyses were conducted using anterior or posterior tooth loss. Results: After controlling for confounders, POS status was associated with tooth loss. The odds ratios (ORs) with A1 as the reference were 1.74 in A2, 2.55 in A3, 3.40 in B1, 4.74 in B2, 5.79 in B3, 6.00 in B4, 4.44 in C1, and 3.00 in C2, respectively. The ORs for anterior tooth loss were higher than those for posterior tooth loss, with the highest OR observed in B4 (21.4). Conclusions: This large population-based cohort study showed that a decreased POS was a risk indicator for tooth loss; furthermore, the risk increased even further in the anterior teeth region

3D Modeling and 3D Materialization of Fluid Art That Occurs in Very Short Time

19th IFIP TC 14 International Conference, ICEC 2020, Xi'an, China, November 10–13, 2020.Proceedings of ICEC2020We have been creating artworks called “liquid art” utilizing liquid dynamics phenomena. One of the liquid artworks is “Sound of Ikebana” which is created by giving sound vibration to color paints and shooting the phenomenon by a high-speed camera, which has been evaluated as “the artwork includes Japanese beauty.” To investigate further why it is evaluated in such a way and also to seek the possibility of its application in society, we tried to materialize it into 3D objects. As the phenomenon occurs in a very short time of less than one second, we have developed a specific experimental environment consisting of multiple high-speed cameras surrounding a speaker where the phenomenon occurs. Among various technologies to reconstruct the 3D model from multiple 2D images, we have chosen a method called Phase-Only Correlation and developed a 3D mesh model of a snapshot of “Sound of Ikebana.” Also using a 3D printer we have successfully obtained 3D materialized “Sound of Ikebana.

Repetitive CREB-DNA interactions at gene loci predetermined by CBP induce activity-dependent gene expression in human cortical neurons

Atsumi Yuri, Iwata Ryohei, Kimura Hiroshi, et al. Repetitive CREB-DNA interactions at gene loci predetermined by CBP induce activity-dependent gene expression in human cortical neurons. Cell Reports 3, 113576 (2023); https://doi.org/10.1016/j.celrep.2023.113576.Neuronal activity-dependent transcription plays a key role in plasticity and pathology in the brain. An intriguing question is how neuronal activity controls gene expression via interactions of transcription factors with DNA and chromatin modifiers in the nucleus. By utilizing single-molecule imaging in human embryonic stem cell (ESC)-derived cortical neurons, we demonstrate that neuronal activity increases repetitive emergence of cAMP response element-binding protein (CREB) at histone acetylation sites in the nucleus, where RNA polymerase II (RNAPII) accumulation and FOS expression occur rapidly. Neuronal activity also enhances co-localization of CREB and CREB-binding protein (CBP). Increased binding of a constitutively active CREB to CBP efficiently induces CREB repetitive emergence. On the other hand, the formation of histone acetylation sites is dependent on CBP histone modification via acetyltransferase (HAT) activity but is not affected by neuronal activity. Taken together, our results suggest that neuronal activity promotes repetitive CREB-CRE and CREB-CBP interactions at predetermined histone acetylation sites, leading to rapid gene expression