記憶型T幹細胞を頂点とした成人T細胞白血病の階層構造の解明

京都大学0048新制・課程博士博士(医学)甲第19267号医博第4031号新制||医||1011(附属図書館)32269京都大学大学院医学研究科医学専攻(主査)教授 小川 誠司, 教授 生田 宏一, 教授 松岡 雅雄学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDGA

Effective gene collection from the metatranscriptome of marine microorganisms

<p>Abstract</p> <p>Background</p> <p>Metagenomic studies, accelerated by the evolution of sequencing technologies and the rapid development of genomic analysis methods, can reveal genetic diversity and biodiversity in various samples including those of uncultured or unknown species. This approach, however, cannot be used to identify active functional genes under actual environmental conditions. Metatranscriptomics, which is similar in approach to metagenomics except that it utilizes RNA samples, is a powerful tool for the transcriptomic study of environmental samples. Unlike metagenomic studies, metatranscriptomic studies have not been popular to date due to problems with reliability, repeatability, redundancy and cost performance. Here, we propose a normalized metatranscriptomic method that is suitable for the collection of genes from samples as a platform for comparative transcriptomics.</p> <p>Results</p> <p>We constructed two libraries, one non-normalized and the other normalized library, from samples of marine microorganisms taken during daylight hours from Hiroshima bay in Japan. We sequenced 0.6M reads for each sample on a Roche GS FLX, and obtained 0.2M genes after quality control and assembly. A comparison of the two libraries showed that the number of unique genes was larger in the normalized library than in the non-normalized library. Functional analysis of genes revealed that a small number of gene groups, ribosomal RNA genes and chloroplast genes, were dominant in both libraries. Taxonomic distribution analysis of the libraries suggests that Stramenopiles form a major taxon that includes diatoms. The normalization technique thus increases unique genes, functional categories of genes, and taxonomic richness.</p> <p>Conclusions</p> <p>Normalization of the marine metatranscriptome could be useful in increasing the number of genes collected, and in reducing redundancies among highly expressed genes. Gene collection through the normalization method was effective in providing a foundation for comparative transcriptomic analysis.</p

Distribution of Air Temperature in Tajimi City in Summer

To research the distribution of air temperature in the city of Tajimi, Gifu prefecture, a total of 15 thermometers were placed at the schools and parks in the city of Tajimi, and the city of Kasugai, Aichi prefecture in August 2010. From the distribution of monthly average air temperature, air temperature at the center of Tajimi city was higher than the suburbs. Also, the days of daily minimum air temperature more than or equal to 25°C and daily maximum air temperature more than or equal to 35°C at the elementary school near the center of Tajimi city was more than those at other schools. This tendency appeared more clearly on the days of daily minimum air temperature more than or equal to 25°C. Also, the air temperature near the center of the city was higher than that ofthe suburbs in the early morning. Thus, it was indicated that the air temperature was hard to decrease as the bottom of the basin. From these results, the influence of urbanization to the formation of the daily minimum temperature in Tajimi city was indicated

Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study

The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at −20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size

Observational Study and Numerical Prediction Experiments on Wet-Bulb Globe Temperature in Tajimi, Gifu Prefecture: Consideration of Uncertainty with a Physics Parameterization Scheme and Horizontal Resolution of the Weather Research and Forecasting Model

As part of research on the actual conditions of the thermal environment surrounding the city of Tajimi, Gifu prefecture, and the city of Kasugai, Aichi prefecture, the surface air temperature and wet-bulb globe temperature (WBGT) were investigated by observation at these locations on clear-sky days in August 2010. Numerical prediction experiments on the WBGT were performed to confirm the utility of the Weather Research and Forecasting (WRF) model. Sensitivity experiments utilizing physics parameterization schemes and horizontal resolution of the WRF model were conducted to confirm the predicted WBGT. The resultsshowed that the maximum sensitivity with the parameterization scheme was 8.4°C for the daytime average, and especially, the simple thermal diffusion surface (SLAB) scheme caused an over/estimation of 6.8°C. On the other hand, the maximum sensitivity with horizontal resolution was 0.5°C, which is much less than that with the parameterization scheme

Acetylation Unleashes Protein Demons of Dementia

Aberrant posttranslational modifications of proteins can impair synaptic plasticity and may render neurons vulnerable to degeneration during aging. In this issue of Neuron, Min et al. show that acetylation of the amino acid lysine in the microtubule-associated protein tau prevents its ubiquitin-mediated degradation, resulting in “tau tangles” similar to those of dementias. Other recent studies suggest that lysine hyperacetylation contributes to the accumulation of amyloid β-peptide in Alzheimer's disease and to impaired cognitive function resulting from a trophic factor deficit

Factors causing climatologically high temperatures in a hottest city in Japan: a multi-scale analysis of Tajimi

In this study, multi-scale climatological features of extreme high temperature (EHT) events in Tajimi, the hottest cities in Japan, were investigated using observational data collected by the Japan Meteorological Agency over the past 23 years, and original data observed by the authors over the last 3 years. Results revealed the background factors that lead to climatologically high temperatures in Tajimi: the occurrence of a characteristic pressure pattern called ‘whale’: the synoptic-scale factors, and the urbanization of Tajimi: the meso-γ-scale factors. In addition, the high temperatures measured in Tajimi are affected by the foehn-like westerly airflow coming from the mountains located in the northwest/west towards the Nobi Plain where Tajimi is located at the east end: the meso-β-scale factors, and the location of the Tajimi observation site, which is within an urbanized area where the highest temperatures tend to be observed: the micro-scale factors. In contrast, statistical analysis demonstrated that the small-scale basin effects and soil dryness around Tajimi were of lesser importance than aforementioned factors, in the occurrence of EHT events in Tajimi

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target