福島第一原発事故が住民の避難行動、周辺地域の救急搬送体制、住民の健康に与えた影響に関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 小林 廉毅, 東京大学特任准教授 山中 崇, 東京大学講師 原田 美由紀, 東京大学講師 山下 英臣, 東京大学講師 岩田 淳University of Tokyo(東京大学

Novel COL11A1 mutation in familial Stickler syndrome

Stickler syndrome (STL) is an autosomal, dominantly inherited, clinically variable and genetically heterogeneous connective tissue disorder characterized by ocular, auditory, orofacial and skeletal abnormalities. We conducted targeted resequencing using a next-generation sequencer for molecular diagnosis of a 2-year-old girl who was clinically suspected of having STL with Pierre Robin sequence. We detected a novel heterozygous missense mutation, NM_001854.3:n.4838G>A [NM_001854.3 (COL11A1_v001):c.4520G>A], in COL11A1, resulting in a Gly to Asp substitution at position 1507 [NM_001854.3(COL11A1_i001)] within one of the collagen-like domains of the triple helical region. The same mutation was detected in her 4-year-old brother with cleft palate and high-frequency sensorineural hearing loss

Removing Diethylphthalate (DEP) from Water Systems using Zeolites and Mesoporous Materials

In order to remove diethylphthalate (DEP) molecules from water systems, zeolites of faujasite (FAU), ferrierite (FER), mordenite (MOR), and mesoporous silica (MCM-41) were employed in this study. 1H nuclear-magnetic-resonance (NMR) spectra showed that FAU was effective in eliminating DEP from aqueous solutions. In addition, solid-state 1H NMR spectra with a magic-angle-spinning (MAS) rate of 30 kHz revealed that a larger amount of DEP was adsorbed on FAUs with higher Si/Al ratios. Our NMR spectra also showed that a chemical shift of the signal assigned to water molecules adsorbed on the FAUs is linked to the amount of DEP adsorption. 1H MAS NMR spectra also revealed that DEP molecules prefer to adsorb on the four-membered ring site rather than the center or/and window of the supercage in FAUs. Since porous materials are frequently present in ground and water systems such as rivers, ponds, and lakes, this study also showed that DEP could adsorb onto soils in aquatic environments and remain in the water system for a long time

Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma

Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment

A novel Stim1-dependent, non-capacitative Ca2+ entry pathway is activated by B cell receptor stimulation and depletion of Ca2+ stores

In most non-excitable cells, the depletion of intracellular Ca2+ stores activates capacitative Ca2+ entry (CCE), which is a Ca2+-selective and La3+-sensitive entry pathway. Here, we report a novel mechanism of La3+-resistant Ca2+ entry that is synergistically regulated by B cell receptor (BCR) stimulation and Ca2+ store depletion (B-SOC). In the wildtype (WT) DT40 cells, BCR stimulation with anti-IgM antibodies induced Ca2+ release and subsequent Ca2+ entry in the presence of 0.3 μMLa3+ which blocks CCE completely. In the inositol 1,4,5-trisphosphate receptor-deficient (IP3R-KO) cells, BCR stimulation elicited neither Ca2+ release nor Ca2+ entry. However, under pretreatment of thapsigargin (ThG), BCR stimulation induced La3+-resistant Ca2+ entry into both WT and IP3R-KO cells. These results indicate that BCR stimulation and Ca2+ store depletion work in concert to activate the La3+-resistant Ca2+ entry pathway. B-SOC was inhibited by tyrosine kinase inhibitor, genistein. In addition, B-SOC was completely abolished in Stim1-deficient cells and was restored by overexpression of yellow fluorescent protein (YFP)-tagged Stim1, but was unaffected by double knockdown of Orai1/Orai2. These results demonstrate a unique non-CCE pathway, in which Ca2+ entry depends on Stim1 and tyrosine kinase activation. It is likely that similar regulation of Ca2+ entry occurs in other cell types including salivary gland cells

Clinical and Functional Significance of Intracellular and Extracellular microRNA-25-3p in Osteosarcoma

Although there is considerable evidence indicating that the dysregulation of microRNAs (miRNAs) in malignant tumors plays a role in tumor development, the overall function of miRNAs and their clinicopathological significance are not well understood. In this retrospective analysis of 45 biopsy specimens from osteosarcoma (OS) patients, we investigated the functional and clinical significance of miR-25-3p in OS, which we previously identified as a highly expressed miRNA in OS patients’ serum. We observed that miR-25-3p dysregulation in human OS tissues was negatively correlated with the clinical prognosis, whereas the expression level of its target gene, Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3), was positively correlated with the clinical prognosis. Endogenous miR-25-3p upregulation promoted tumor growth, invasion, and drug resistance, which was consistent with DKK3 silencing in OS cells. In addition, secretory miR-25-3p was embedded in tumor-derived exosomes, where it promoted capillary formation and the invasion of vascular endothelial cells. Overall, our results show that miR-25-3p has intracellular and extracellular oncogenic functions as well as clinicopathological relevance in OS, indicating its potential as a novel diagnostic and therapeutic tool for the clinical management of this disease

Defining and Acting on Global Health: The Case of Japan and the Refugee Crisis

What counts as global health? There has been limited discourse to date on the ways in which country-level contexts may shape positioning in global health agendas. By reviewing Japan’s response to the refugee crisis, we demonstrate a clash between rhetoric and action on global responsibility, and suggest that cultural and historical factors may be related to the ways of perceiving and acting upon global health