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Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice
Get PDF三重大学博士(医学)application/pdfA clinical challenge remains in the treatment of hypoxic–ischemic brain injury in newborns. Nicotinamide adenine dinucleotide (NAD+) has beneficial effects in animal models of adult stroke. Here, we aimed to understand the short- and long-term neuroprotective effects of NAD+-promoting substance nicotinamide mononucleotide (NMN) in a well-established brain injury model in neonatal mice. Postnatal day (PND) 9 male and female mice were subjected to cerebral hypoxia–ischemia and treated with saline or NMN (50 mg/kg) immediately after hypoxia–ischemia. At different time points after hypoxia–ischemia, hippocampal NAD+, caspase-3 activity, protein expression of SIRT1, SIRT6, release of high mobility group box-1 (HMGB1), long-term neuropathological outcome, short-term developmental behavior, and long-term motor and memory function were evaluated. Neonatal hypoxia–ischemia reduced NAD+ and SIRT6 levels, but not SIRT1, in the injured hippocampus, while HMGB1 release was significantly increased. NMN treatment normalized hippocampal NAD+ and SIRT6 levels, while caspase-3 activity and HMGB1 release were significantly reduced. NMN alleviated tissue loss in the long-term and improved early developmental behavior, as well as motor and memory function. This study shows that NMN treatment provides neuroprotection in a clinically relevant neonatal animal model of hypoxia ischemia in mice suggesting as a possible novel treatment for neonatal brain injury.本文/Department of Obstetrics and Gynecology, Mie University, Tsu, Japan18pdoctoral thesi
Intake of allergenic foods at 1.5 years and 3 years of age in a general child population in Japan: a crosssectional study
Get PDF三重大学博士(医学)application/pdfbackground: Recent studies indicate that the timing of introduction of potentially allergenic food is crucial for the development of food allergy in children. This cross-sectional study aimed to clarify the reality of allergen food intake in a general population of young children in Japan.
Methods: A questionnaire survey of caregivers was conducted at health checkups for 1.5-year (18-month)-old and 3-year-old children in the fall of 2020. The caregivers were asked about (I) the presence/absence of allergic disease symptoms based on the ISAAC questionnaire, and (2) foods that caregivers avoided giving their children. Ordinal logistic regression analyses were periformed to determine factors associated with food avoidance.
Results: Questionnaires were distributed to 1720 caregivers, and 1603 (93%) responded. The responders consisted of 771 and 832 caregivers who participated in 1.5-year-old and 3-year-old checkups, respectively. The prevalence of allergic diseases was comparable to recent epidemiological studies in Japan, indicating that the population may be representative. At 1.5 years old, more than 50% of the children were not exposed to peanuts, tree nuts, fish eggs, shellfish, and buckwheat. At 3 years old, the avoidance rates of the foods had decreased but were still between 18.8% and 32.0%. On the other hand, the avoidance rates of chicken egg and cow’s milk, the top 2 common allergenic foods in Japan, were much lower at 2.8% and 1.5% at 1.5 years, and they decreased to 1.4% and 0.7% at 3 years old, respectively. Ordinal logistic analysis showed that avoidance of chicken egg, cow’s milk, and wheat was associated with food allergy diagnosis and chicken egg avoidance with eczema, but avoidance of other foods showed no associations with any risk factors for food allergy.
Conclusion: Caregivers avoided giving various foods, independent of allergy risk factors, to their young children. Since delayed introduction of an allergenic food has been reported to increase the risk of developing an allergy to the food, the results warrant future investigation of the development of food allergies in relation to current eating habits and recommendations.本文/Allergy Center and Department of Clinical Research, Naitonal Hospital Organization Mie National Hospital12pdoctoral thesi
思春期にある子どもの1型糖尿病管理に関する研究
Get PDF三重大学博士(看護学)application/pdf要約/三重大学大学院医学系研究科 看護学専攻（博士後期課程）看護学領域 母子看護学分野thesi
Development of non-invasive age estimation methods andecological studies on post-reproductive females in Indo-Pacific bottlenose dolphins
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Development of sake and craft beer using regionalresources
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IEEE802.11ネットワークにおける強化学習に基づくキャリアセンス閾値制御に関する研究
Get PDFapplication/pdf三重大学大学院工学研究科 電気電子工学専攻 通信工学研究室61pthesi
Bahcc1 is critical for the aberrant epigenetic program in a mouse model of MLL-ENL -mediated leukemia
Get PDF三重大学博士(医学)application/pdfIn leukemogenesis, genotoxic stress in hematopoietic stem and progenitor cells (HSPCs) drives individual context-dependent programs of malignant transformation. In light of the various differentiation stages of HSPCs based on a recently revised definition using CD150/CD48, our analyses showed that a subpopulation of long-term repopulating HSCs was most susceptible to MLL-ENL–mediated transformation. An analysis of the molecular mechanism identified Bromo-adjacent homology domain and coiled-coil containing 1 (Bahcc1), which encodes a reader molecule of trimethylated histone H3 lysine 27 (H3K27me3), as a candidate gene involved in distinct susceptibility to leukemic transformation. Interestingly, Bahcc1 was previously reported to be highly expressed in acute myeloid leukemia (AML) with an unfavorable prognosis, including some cases of MLL-rearranged AML. We found that MLL-ENL upregulated Bahcc1 through binding to its promoter, and that Bahcc1 was involved in MLL-ENL–mediated immortalization at least partly through repression of H3K27me3-marked Cdkn1c. Analyses using bone marrow transplantation in mice showed that depletion of Bahcc1 suppressed the leukemogenic activity of MLL-ENL. In a public database, high BAHCC1 expression was found to be associated with a poor prognosis in pediatric AML, in which BAHCC1 expression was significantly lower in MLL-AF9-AML than in other MLL-fusion-AML. These findings shed light on the distinct immortalization potential of HSPCs and suggest a novel MLL-fusion-Bahcc1 axis, which may lead to development of molecular targeted therapy against MLL-fusion–mediated leukemia.本文/Department of Microbiology and Molecular Genetics and Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan30pdoctoral thesi
Evaluation of the effects of mutation in the wheat AP2 homoeologs on the potential for cleistogamous flowering
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Evaluation of the effects of mutation in the wheat AP2 homoeologs on the potential for cleistogamous flowering
Get PDF三重大学博士(学術)application/pdfCleistogamy or fertilization in closed flowers reduces the risk of fungal infection of the florets at anthesis in Triticeae crops. Cleistogamy in barley (Hordeum vulgare) is determined by a single recessive gene at the Cleistogamy1 (Cly1) locus on chromosome 2H. The Cly1 gene is known to be the barley ortholog of the Arabidopsis Apetala2 (AP2) transcription factor gene. A point mutation within the microRNA172 (miR172) target site of Cly1 inhibits the binding of miR172 to the target site of the mRNA, resulting in the production of the Cly1 (HvAP2) protein. This protein negatively regulates the development of lodicules, keeping florets closed at anthesis. However, cleistogamy is not evident in hexaploid wheat (Triticum aestivum) cultivars. The aim of this study is to develop a cleistogamous wheat which could evade the infection caused by Fusarium head blight and to minimize pollen-mediated gene flow. The present study focused on evaluating the effects of mutations in the wheat AP2 homoeologs on the potential for cleistogamous flowering.
The initial objective was to identify newly induced mutations in the wheat AP2 homoeologs, the three homoeologous genes (AP2-A, AP2-B and AP2-D) located on chromosomes 2A, 2B and 2D. The AP2 mutants were induced from the Japanese winter wheat cultivar 'Kitahonami' by ethyl methanesulfonate (EMS) treatment of the seeds. Three independent mutants carrying novel point mutations within the miR172 target site in AP2-A and AP2-D were identified and the mutant alleles were designated as AP2-A1, AP2-D1 and AP2-D2. However, no point mutations within the miR172 target site were detected in AP2-B. These point mutations were distinct from those identified in the cleistogamous alleles cly1.b and cly1.c of the orthologous barley Cly1 gene. Field observations showed normal flowering in all mutants. The lodicules of the mutants swelled during anthesis, however, their sizes exhibited notable variations compared to the wild type. Lodicule depth was decreased in all three mutants, with AP2-D2 exhibiting the greatest reduction. Lodicule length and width showed a similar trend in AP2-D2, however, not in AP2-A1 or AP2-D1. Furthermore, AP2-D2 had much shorter (compact) spikes compared to AP2-A1 and AP2-D1. The reduced spike length was due to a significant reduction in the length of the rachis (spike) internode. Reduced interaction between mRNA and miR172 at the target site of AP2-D2 resulted in higher transcript levels that suppressed lodicule development and rachis internode elongation.
A proposed strategy to develop cleistogamous wheat is to accumulate the point mutations in all three AP2 homoeologs. This study provided insights into the cumulative effects of mutant AP2 alleles in suppressing open flowering. A precise evaluation of the effects of the mutations was made using near-isogenic lines (NILs). Three single mutants (AP2-A1, AP2-D1 and AP2-D2) with two double mutants (AP2-A1/AP2-D1 and AP2- A1/AP2-D2) were evaluated for the effects on flowering and other agronomic traits under near-isogenic background. Among the three single mutant alleles, AP2-D2 had the greatest effect on reducing the rate of anther extrusion. Furthermore, the double mutant AP2-A1/AP2-D2 inhibited anther extrusion more than the single mutant AP2-D2. Similarly, AP2-D2 had the greatest effect on reducing lodicule depth, whereas AP2- A1/AP2-D2 showed a significantly greater reduction in lodicule depth than AP2-D2. AP2-D2 had an additive effect on reducing rachis (spike) internode length, although both AP2-A1 and AP2-D1 also had an effect, but less than AP2-D2. The double mutant AP2- A1/AP2-D1 had a stronger effect on reducing rachis internode length than either AP2-A1 or AP2-D1, indicating the cumulative effect of these two alleles. In addition, both single and double mutants carrying the AP2-D2 allele had shorter culm lengths due to its reduced internode length, suggesting its pleiotropic effect on stem elongation. The AP2-D2 allele showed higher expression levels than the wild type in several floral organs as well as in the rachis and culm.
In conclusion, AP2-A1/AP2-D2 was evaluated as the most effective genotype in suppressing flower opening, although cleistogamy was not achieved. The study also provided new insights into the pleiotropic effects of individual mutant AP2 alleles on plant development and agronomic traits in wheat.本文97pdoctoral thesi
