Mutant analyses reveal different functions of fgfr1 in medaka and zebrafish despite conserved ligand–receptor relationships

AbstractMedaka (Oryzias latipes) is a small freshwater teleost that provides an excellent developmental genetic model complementary to zebrafish. Our recent mutagenesis screening using medaka identified headfish (hdf) which is characterized by the absence of trunk and tail structures with nearly normal head including the midbrain–hindbrain boundary (MHB). Positional-candidate cloning revealed that the hdf mutation causes a functionally null form of Fgfr1. The fgfr1hdf is thus the first fgf receptor mutant in fish. Although FGF signaling has been implicated in mesoderm induction, mesoderm is induced normally in the fgfr1hdf mutant, but subsequently, mutant embryos fail to maintain the mesoderm, leading to defects in mesoderm derivatives, especially in trunk and tail. Furthermore, we found that morpholino knockdown of medaka fgf8 resulted in a phenotype identical to the fgfr1hdf mutant, suggesting that like its mouse counterpart, Fgf8 is a major ligand for Fgfr1 in medaka early embryogenesis. Intriguingly, Fgf8 and Fgfr1 in zebrafish are also suggested to form a major ligand–receptor pair, but their function is much diverged, as the zebrafish fgfr1 morphant and zebrafish fgf8 mutant acerebellar (ace) only fail to develop the MHB, but develop nearly unaffected trunk and tail. These results provide evidence that teleost fish have evolved divergent functions of Fgf8–Fgfr1 while maintaining the ligand–receptor relationships. Comparative analysis using different fish is thus invaluable for shedding light on evolutionary diversification of gene function

有機フッ素化合物曝露と子どもの健康 : 子どもの健康と環境に関する北海道スタディ

サステナブルで安心な社会の構築へ向けて : 予防原則という考え方(Towards a Safe and Sustainable Society : Applicability of the Precautionary Perspective)　2013年11月5日. 北海道大学学術交流会館小講堂 , 札幌市

The feasibility of aromatherapy massage to reduce symptoms of Idiopathic Environmental Intolerance : A pilot study

Objectives: Idiopathic Environmental Intolerance (IEI) is an acquired disorder with multiple recurrent symptoms, which is associated with diverse environmental factors that are tolerated by the majority of people. IEI is an illness of uncertain aetiology, making it difficult to treat using conventional medicine. Therefore, there is a need for novel therapies to control the symptoms of IEI. The objective of this study was to evaluate the feasibility and impact of aromatherapy massage for individuals with IEI. Design: Non-blinded crossover trial Setting: IEI patients who attended a clinic in Sapporo city were recruited, and sixteen patients were enrolled. Participants were clinically examined by an experienced medical doctor and met the criteria included in the working definition of IEI disorder. Interventions: During the active period, participants received four one-hour aromatherapy massage sessions every two weeks. During the control period, the participants did not receive any massages. Main outcome measurements: Scores on the IEI-scales trigger checklist, symptoms, life impact, and the State Anxiety Inventory were assessed before and after each period. Short-term mood enhancement was evaluated using the Profiles of Mood Status (POMS) before and after sessions. Results: Due to period effects, evaluation of the results had to be restricted to the first period, and the result showed no effect of intervention. All six sub-scales of the POMS improved after each session. (mean score differences: 4.89 to 1.33, p<0.05). Conclusions: Aromatherapy was well tolerated by subjects with IEI; however, aromatherapy, as applied in this study, did not suggest any specific effects on IEI condition

The relationship between atopic dermatitis and indoor environmental factors : a cross-sectional study among Japanese elementary school children

Objectives: This study aimed to determine that home environmental factors were associated with atopic dermatitis in Japanese elementary school children. Methods: In this cross-sectional study, a total of 4,254 children in 12 public elementary schools in Sapporo city in Hokkaido, Japan were examined. Atopic dermatitis was defined using the International Study of Asthma and Allergies in Childhood questionnaire. The questionnaires also contained 14 questions about the child’s home environment. To obtain multivariate-adjusted ORs for atopic dermatitis in relation to the home environment, we controlled for possible confounders including gender, school grade, parental history of allergies, number of siblings, and whether the child was firstborn. The study participants were then divided into two groups according to gender, and a stratified analysis was performed to obtain adjusted ORs for atopic dermatitis in relation to the home environment. Results: The prevalence of atopic dermatitis in our sample was 16.7 %. Using fully adjusted models, the risk factors for atopic dermatitis were found to be the household use of a non-electric heating system without a ventilation duct to the outside (compared to the use of an electric heating system), having visible mould in the house, having a mouldy odour in the house, and condensation on the windowpanes in the house odds ratios (OR 1.25–1.54). In our stratified analysis, having visible mould and having a mouldy odour in the house were relevantly found to be risk factors for boys (OR 1.28–1.64). However, these associations were not found among girls. Conclusions: To improve children’s health, further study is needed to corroborate the findings

Birth cohorts in Asia : The importance, advantages, and disadvantages of different-sized cohorts

Asia contains half of the world's children, and the countries of Asia are the most rapidly industrializing nations on the globe. Environmental threats to the health of children in Asia are myriad. Several birth cohorts were started in Asia in early 2000, and currently more than 30 cohorts in 13 countries have been established for study. Cohorts can contain from approximately 100-200 to 20,000-30,000 participants. Furthermore, national cohorts targeting over 100,000 participants have been launched in Japan and Korea. The aim of this manuscript is to discuss the importance of Asian cohorts, and the advantages and disadvantages of different-sized cohorts. As for case, one small-sized (n = 514) cohort indicate that even relatively low level exposure to dioxin in utero could alter birth size, neurodevelopment, and immune and hormonal functions. Several Asian cohorts focus prenatal exposure to perfluoroalkyo substances and reported associations with birth size, thyroid hormone levels, allergies and neurodevelopment. Inconsistent findings may possibly be explained by the differences in exposure levels and target chemicals, and by possible statistical errors. In a smaller cohort, novel hypotheses or preliminary examinations are more easily verifiable. In larger cohorts, the etiology of rare diseases, such as birth defects, can be analyzed; however, they require a large cost and significant human resources. Therefore, conducting studies in only one large cohort may not always be the best strategy. International collaborations, such as the Birth Cohort Consortium of Asia, would cover the inherent limitation of sample size in addition to heterogeneity of exposure, ethnicity, and socioeconomic conditions

Secular trends of urinary phthalate metabolites in 7-year old children and association with building characteristics : Hokkaido study on environment and children's health

The widespread commercial production and use of phthalates as plasticizers in consumer products have led to significant human exposure. Some phthalates are known to disrupt the endocrine system and result in adverse health outcomes. As such, they have been regulated in materials used for children?s items and food packages. In this study, we examined the secular trend of urinary phthalate metabolites in children and the association between metabolites and building characteristics. In total, 400 first-morning spot urine samples of 7 years old children collected from 2012 to 2017 from an ongoing birth cohort study were examined. Parents provided information on demographics and building questionnaires. We analyzed 10 urinary phthalate metabolites from five phthalate diesters using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/ MS): MiBP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MECPP, MiNP, OH-MiNP, and cx-MiNP. A multivariable regression model with creatinine-corrected metabolite levels was applied to assess secular trends during 2012?2017. The association between metabolite levels and building characteristics was investigated using a mutual-adjusted linear regression. The metabolites MnBP, MEHP, MEOHP, MEHHP, MECPP, and OH-MiNP were detected in all samples. The highest median concentration was for MECPP 37.4 ng/mL, followed by MnBP and MEHHP at concentrations of 36.8 and 25.8 ng/mL, respectively. Overall, DBP, BBzP, and DINP metabolite concentrations in this study were comparable to or lower than those in previous studies from Japan and other countries in a similar study period. Higher concentrations of DEHP metabolites were observed in this study than in children from the USA and Germany, as per previous reports. Despite updated phthalate regulations and reports of production volume change in Japan, all the measured metabolites showed a stable trend between 2012 and 2017. Higher phthalate metabolite levels were observed among children from households with low annual income, those who lived in old buildings, and those with window opening habits of ?1 h than <1 h. In contrast, children in houses that vacuumed 4 or more days/week showed a lower level of MnBP than those in houses that vacuumed <3 days/ week. This study demonstrates that the internal exposure level of phthalates in Japanese children was stable from 2012 to 2017. Our findings suggest that phthalate exposure in children is consistent. Thus, improvements in the indoor environment, such as frequent vacuuming, may reduce exposure. Biomonitoring of phthalates is critical for elucidating their possible health effects and developing mitigation strategies

Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size : The Hokkaido study on environment and children's health

Di-2-ethylhexyl phthalate (DEHP) is one of the most widely used phthalates. Metabolites of DEHP are detectable in majority of the population. Findings on adverse health outcomes, particularly birth weight in association with prenatal exposure to DEHP remain equivocal. Besides, there is insufficient evidence to address influence on metabolic function from epidemiological studies. Thus, our objective was to investigate cord blood adipokine levels and birth size in association with prenatal DEHP exposure in prospective birth cohort study. Mono-2-methylhexyl phthalate (MEHP), primary metabolite of DEHP was determined as exposure by using maternal blood sample of 3rd trimester. Leptin and adiponectin levels in cord blood were measured as markers of metabolic function. Birth weight and length were obtained from birth record. Association between maternal MEHP levels and cord blood adiponectin and leptin levels, birth weight and ponderal index (PI) were examined for 167 mother-child pairs who had both MEHP and cord blood adipokine measurements. The median MEHP level was 8.81 ng/ml and the detection rate was 100%. There was no sex difference in MEHP levels. Both leptin and adiponectin levels were higher in girls than in boys. MEHP level was positively associated with adiponectin level among boys and was negatively associated with leptin level among girls. MEHP level were negatively associated with PI only in girls and this could be due to decreased leptin level. This study suggested that prenatal DEHP exposure may be associated with cord blood adipokine and birth size. The influence potentially be sex-specific and could be more significant in girls