海洋性有害赤潮形成藻類Heterosigma akashiwoが原核生物群集に及ぼす影響に関する分子生態学的研究

京都大学新制・課程博士博士(農学)甲第24677号農博第2560号新制||農||1100(附属図書館)学位論文||R5||N5458(農学部図書室)京都大学大学院農学研究科応用生物科学専攻(主査)教授 吉田 天士, 教授 澤山 茂樹, 准教授 神川 龍馬学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDGA

Content-based CT image retrieval system using deep learning: Preliminary assessment of its accuracy for classifying lesion patterns and retrieving similar cases among patients with diffuse lung diseases

Practical image retrieval systems must fully use image databases. We investigated the accuracy of our content-based computer tomography (CT) image retrieval system (CB-CTIRS) for classifying lesion patterns and retrieving similar cases in patients with diffuse lung diseases. The study included 503 individuals, with 328 having diffuse lung disease and 175 having normal chest CT scans. Among the former, we randomly selected ten scans that revealed one of five specific patterns [consolidation, ground-glass opacity (GGO), emphysema, honeycombing, or micronodules: two cases each]. Two radiologists separated the squares into six categories (five abnormal patterns and one normal pattern) to create a reference standard. Subsequently, each square was entered into the CB-CTIRS, and the F-score used to classify squares was determined. Next, we selected 15 cases (three per pattern) among the 503 cases, which served as the query cases. Three other radiologists graded the similarity between the retrieved and query cases using a 5-point grading system, where grade 5 = similar in both the opacity pattern and distribution and 1 = different therein. The F-score was 0.71 for consolidation, 0.63 for GGO, 0.74 for emphysema, 0.61 for honeycombing, 0.15 for micronodules, and 0.67 for normal lung. All three radiologists assigned grade 4 or 5 to 67.7% of retrieved cases with consolidation, emphysema, or honeycombing, and grade 2 or 3 to 67.7% of the retrieved cases with GGO or micronodules. The retrieval accuracy of CB-CTIRS is satisfactory for consolidation, emphysema, and honeycombing but not for GGO or micronodules

Expression and Role of IL-1β Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing

The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1β (IL-1β) signal is an important major factor in fracture healing, whereas its relevance to retinoid receptor (an RAR inverse agonist, which promotes endochondral bone formation) remains unclear. Herein, we investigated the expressions of IL-1β and retinoic acid receptor gamma (RARγ) in a rat fracture model and the effects of IL-1β in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1β and RARγ were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1β decreases the levels of aggrecan and type II collagen but significantly increased the metalloproteinase-13 (Mmp13) mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. An RAR inverse agonist (AGN194310) inhibited IL-1β-stimulated Mmp13 and Ccn2 mRNA in a dose-dependent manner. Phosphorylated extracellular signal regulated-kinases (pERK1/2) and p-p38 mitogen-activated protein kinase (MAPK) were increased time-dependently by IL-1β treatment, and the IL-1β-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1β-stimulated expressions of Mmp13 and Ccn2 mRNA. MMP13, CCN2, and p-p38 MAPK were expressed in hypertrophic chondrocytes near the invaded vascular endothelial cells. As a whole, these results point to role of the IL-1β via p38 MAPK as important signaling in the regulation of the endochondral bone formation in fracture healing, and to the actions of RAR inverse agonists as potentially relevant modulators of this process

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Sonic Hedgehog Regulates Bone Fracture Healing

Bone fracture healing involves the combination of intramembranous and endochondral ossification. It is known that Indian hedgehog (Ihh) promotes chondrogenesis during fracture healing. Meanwhile, Sonic hedgehog (Shh), which is involved in ontogeny, has been reported to be involved in fracture healing, but the details had not been clarified. In this study, we demonstrated that Shh participated in fracture healing. Six-week-old Sprague–Dawley rats and Gli-CreERT2; tdTomato mice were used in this study. The right rib bones of experimental animals were fractured. The localization of Shh and Gli1 during fracture healing was examined. The localization of Gli1 progeny cells and osterix (Osx)-positive cells was similar during fracture healing. Runt-related transcription factor 2 (Runx2) and Osx, both of which are osteoblast markers, were observed on the surface of the new bone matrix and chondrocytes on day seven after fracture. Shh and Gli1 were co-localized with Runx2 and Osx. These findings suggest that Shh is involved in intramembranous and endochondral ossification during fracture healing

Viral Nature of the Aquatic Ecosystems

Part of the Advances in Environmental Microbiology book series (AEM, volume 9)Viruses infecting microorganisms are ubiquitous and highly abundant in aquatic environments. They considerably affect the dynamics, diversity, and evolution of their host microorganisms. In this review, we discuss the ecological implications of viruses from the perspectives of the biogeochemical cycles, microbial diversity, and virus–host coevolutionary dynamics in aquatic environments. Generally, viruses redirect host metabolism toward reproduction through molecular host–virus interactions characterized by the compositional and stoichiometric changes in intracellular metabolites, which are eventually released into the environment when the infected host cells are lysed, thus also changing the chemical composition of the water. Therefore, the modulation of metabolite biosynthesis and promotion of their recycling are major viral functions. Viruses also maintain microbial community diversity via increased infection and lysis rates of the dominant taxa and genotypes in a frequency-dependent manner, thereby allowing the co-existence of members with various competitive abilities. Finally, viruses can expand their own genotypic diversity and that of the host through complex defense and counter-defense interactions, including loss of host fitness due to the cost of resistance and the possible need for antiviral defense-specific (e.g., intra- vs. extracellular) changes in the hosts genome diversification. Continuous interactions drive the coevolution of hosts and viruses, thereby increasing both the host and viral micro-diversity. Hence, these fundamental functions are viral “raison d’etre” and are essential for the functioning of aquatic ecosystems and its components

Sonic Hedgehog Signaling and Tooth Development

Sonic hedgehog (Shh) is a secreted protein with important roles in mammalian embryogenesis. During tooth development, Shh is primarily expressed in the dental epithelium, from initiation to the root formation stages. A number of studies have analyzed the function of Shh signaling at different stages of tooth development and have revealed that Shh signaling regulates the formation of various tooth components, including enamel, dentin, cementum, and other soft tissues. In addition, dental mesenchymal cells positive for Gli1, a downstream transcription factor of Shh signaling, have been found to have stem cell properties, including multipotency and the ability to self-renew. Indeed, Gli1-positive cells in mature teeth appear to contribute to the regeneration of dental pulp and periodontal tissues. In this review, we provide an overview of recent advances related to the role of Shh signaling in tooth development, as well as the contribution of this pathway to tooth homeostasis and regeneration