Role of PERK in mitochondrial function

Mitochondria play a central role in the function of brown adipocytes (BAs). Although mitochondrial biogenesis, which is indispensable for thermogenesis, is regulated by coordination between nuclear DNA transcription and mitochondrial DNA transcription, the molecular mechanisms of mitochondrial development during BA differentiation are largely unknown. Here, we show the importance of the ER-resident sensor PKR-like ER kinase (PERK) in the mitochondrial thermogenesis of brown adipose tissue. During BA differentiation, PERK is physiologically phosphorylated independently of the ER stress. This PERK phosphorylation induces transcriptional activation by GA-binding protein transcription factor α subunit (GABPα), which is required for mitochondrial inner membrane protein biogenesis, and this novel role of PERK is involved in maintaining the body temperatures of mice during cold exposure. Our findings demonstrate that mitochondrial development regulated by the PERK–GABPα axis is indispensable for thermogenesis in brown adipose tissue

Study on the way of educational practical training of special needs education in at the special needs class in the affiliated school, Hiroshima Univerisity

本研究は，附属学校の特別支援学級における教育実習において，実習終了後に行う公立特別支援学校での教育実習のさらなる充実を図り，学部の教育と附属の実習，公立特別支援学校での実習の連続性整備のためにプログラムの見直しや改善を図ると共に，そのあり方について検討する。附属東雲小学校・中学校は大学の特別支援教育学講座と連携し，教育実習の内容の検討や改善に向けての提言を受ける他，具体的な大学における取り組みとも連動するようにした。さらに，特別支援教育実習協議会を通して特別支援学校との連携を図り，実習校と学生へのアンケート調査によって課題を明らかにした。また，全国の附属学校特別支援学級の連絡協議会を活用し，教育実習における実情や課題を情報交換することで、情報の共有化を図り新たな知見も得た。このような取り組みを進めていく中で，実習の事前指導にあたり，公立特別支援学校との連携が不足していたことが課題としてあげられた。この課題を解決していくために，教育実習に対しての附属学校としての取り組みを改善すると共に，より具体的かつ実用的な指導や評価を行い，内容を引き継ぐシステムの構築が必要であることが明らかとなった。The purpose of this research is to improve the teaching practice at the public special support school which is carried out after completion of the educational practice of the attached school special support class and to improve the educational practice of the undergraduate school and the special special support school We reviewed the contents of teaching practice and examined improvement. Attached Shinonome Elementary School and Junior High School have a special support education course lecture of the Graduate school of pedagogy and a public education practice meeting with the public special support school, and from the questionnaire survey to each school and the student, lack of cooperation with the public special support school It was made clear that it was. In order to solve the problem, it is necessary to instruct teacher interns more practical guidance and evaluation, and to inherit the contents to the public special support school

Serological diagnosis of allergic bronchopulmonary mycosis: Progress and challenges

Prompt diagnosis of allergic bronchopulmonary mycosis (ABPM) is an important clinical issue in preventing irreversible lung damage. Therefore, a good serological marker for the diagnosis of ABPM is desired in clinical practice. The measurement of IgE antibody to crude Aspergillus fumigatus allergen is considered the first step in screening asthmatic patients for allergic bronchopulmonary aspergillosis (ABPA). However, presence of IgE to A. fumigatus does not always indicate genuine sensitization to A. fumigatus because of cross-reactivity between crude extracts from different fungal sources. The application of molecular-based allergy diagnosis can solve this problem. The specificity of testing can be greatly improved by measuring the IgE antibody to Asp f 1 and f 2, specific allergen components for genuine A. fumigatus allergy. The problem of cross-reactivity between crude fungal extracts is also true for the identification of genuine causal fungi in each ABPM patient. Some patients with ABPM induced by fungi other than Aspergillus may be consistent with ABPA diagnostic criteria because current criteria depend on IgE/IgG reactivity to crude extracts. Accurate identification of genuine causal fungi for ABPM is of clinical importance, considering that clinical presentation, anti-fungal treatment strategies and disease prognosis can be influenced by different causal fungi. The diagnosis of causal fungi can be robustly validated by the confirmation of genuine sensitization to fungi after measuring IgE to specific allergen components, as well as repeated microbiological isolation of the fungi from their airway

Detection of Antilymphocyte Antibody with Two-Color Method in Systemic Lupus Erythematosus and Its Heterogeneous Specificities against Human T-Cell Subsets

The two-color method originally described by Van Rood et al. (Van Rood, J. J., A. Van Leeuwen, and J. S. Ploen. 1976. Simultaneous detection of two cell populations by two-color fluorescence and application to the recognition of B-cell determinants. Nature (Lond.). 262: 795-797) for the typing of homologous leukocytic antibodies, D-region was used for the detection of antilymphocyte antibody (ALA) in systemic lupus erythematosus. In this method, surface immunoglobulin-bearing cells were identified with fluorescein isothiocyanate-labeled anti-immunoglobulin and nuclei of killed cells were stained with ethidium bromide. Therefore, cell type (T or B) of the target cells can be identified without fractionating them. ALA was detected in 87% of lupus sera and had a preferential reactivity with T cells. Its major immunoglobulin class was shown to be immunoglobulin (Ig)M. The subspecificity of ALA was further analyzed using fractionated T-cell subsets as target cells. When T lymphocytes were separated into Fc receptor-bearing (Tγ) and lacking (Tγ[-]) cells, 64% of ALA showed preferential reactivity with Tγ cells and 14% with Tγ(-) cells. The remainder had no selective reactivity against Tγ or Tγ(-) cells. Tγ cells were shown to have suppressor activity, whereas Tγ(-) cells were indicated to contain helper cells. The above finding was in agreement with the observation that treatment of T cells with ALA that preferentially react with Tγ cells considerably enhanced immunoglobulin synthesis in vitro, whereas treatment of T cells with ALA reactive with Tγ(-) cells clearly suppressed the formation of immunoglobulins. Treatment of ALA with no selective reactivity showed variable effects on in vitro immunoglobulin synthesis. These results indicate that ALA in lupus have heterogeneous specificities against human T-cell subsets

Persistent Airflow Obstruction in Young Adult Asthma Patients

Background: Lung function determined by spirometry and the severity of dyspnea correlate weakly in asthma patients. We attempted to determine the risk factors in asthma patients having persistent airway obstruction despite of having only mild subjective symptoms, and to examine the possibility of improving FEV1 by treating asthma on the basis of the bronchodilator change in FEV1. Methods: We examined asthma patients in their 20s and who visited Sagamihara National Hospital for the first time over a period of four years, by reviewing their clinical records. They underwent tests on the bronchodilator change in FEV1 and a test of airway hyperresponsiveness to histamine dihydrochloride. Results: One hundred thirty-eight subjects (mean age, 25.6 years; 51 males, 87 females; current smoking, 30.4%; history of childhood asthma, 48.6%) were enrolled. Among them, 18.8% (26/138) showed persistent airway obstruction (postbronchodilator FEV1/FVC (%) <80%). Using the multiple logistic regression model, we found that history of childhood asthma and smoking history were the significant isolated risk factors for persistent airway obstruction. Moreover, we determined that the factors associated with the reversibility of airway obstruction in asthma patients without subjective symptoms were history of childhood asthma. Conclusions: In this study, patients not undergoing treatment for asthma were examined. History of childhood asthma and smoking history may be the risk factors for persistent airway obstruction in the asthma patients with mild subjective symptoms. Tests on the bronchodilator change in FEV1 should be performed in patients with history of childhood asthma and smoking history, even if they have only mild subjective symptoms