Sufficient Capability and Sufficient Distribution : Examining Relationship between Them

書評企画２森悠一郎（2019）『関係の対等性と平等』弘文

Impaired response of hypoxic sensor protein HIF-1 alpha and its downstream proteins in the spinal motor neurons of ALS model mice

We have recently reported spinal blood flow-metabolism uncoupling in an amyotrophic lateral sclerosis (ALS) animal model using Cu/Zn-superoxide dismutase 1 (SOD1)-transgenic (Tg) mice, suggesting a relative hypoxia in the spinal cord. However, the hypoxic stress sensor pathway has not been well studied in ALS. Here, we examined temporal and spatial changes of the hypoxic stress sensor proteins HIF-1 alpha and its downstream proteins (VEGF, HO-1, and EPO) during the normcodccourse of motor neuron (MN) degeneration in the spinal cord of these ALS model mice. We found that HIP-1 alpha protein expression progressively increased both in the anterior large MNs and the surrounding glial cells in Tg mice from early symptomatic 14 week (W) and end stage 18W. Double immunofluorescence analysis revealed that HIP-1 alpha, plus GFAP and Iba-1 double-positive surrounding glial cells, progressively increased from 14 W to 18 W, although the immunohistochemistiy in large MNs did not change. Expression levels of VEGF and HO-1 also showed a progressive increase but were significant only in the surrounding glial cells at 18W. In contrast, EPO protein expression was decreased in the surrounding glial cells of Tg mice at 18W. Because HIF1-alpha serves as an important mediator of the hypoxic response, these findings indicate that MNs lack the neuroprotective response to hypoxic stress through the HIF-1 alpha system, which could be an important mechanism of neurodegeneration in ALS

Dose-response relationship between sports activity and musculoskeletal pain in adolescents.

Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose-response relationship between sports activity and MSP among adolescents. Two school-based serial surveys were conducted 1 year apart in adolescents aged 12 to 18 years in Unnan, Japan. Self-administered questionnaires were completed by 2403 students. Associations between time spent in organized sports activity and MSP were analyzed cross-sectionally (n = 2403) and longitudinally (n = 374, students free of pain and in seventh or 10th grade at baseline) with repeated-measures Poisson regression and restricted cubic splines, with adjustment for potential confounders. The prevalence of overall pain, defined as having pain recently at least several times a week in at least one part of the body, was 27.4%. In the cross-sectional analysis, sports activity was significantly associated with pain prevalence. Each additional 1 h/wk of sports activity was associated with a 3% higher probability of having pain (prevalence ratio = 1.03, 95% confidence interval = 1.02-1.04). Similar trends were found across causes (traumatic and nontraumatic pain) and anatomic locations (upper limbs, lower back, and lower limbs). In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P < 0.001) but not a nonlinear association (P ≥ 0.45). The more the adolescents played sports, the more likely they were to have and develop pain.This study was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. MK is supported by a JSPS Postdoctoral Fellowship for Research Abroad. FI is supported by the Medical Research Council Epidemiology Unit (MC_UU_12015/1; MC_UU_12015/5).This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1097/j.pain.000000000000052

Sp6 downregulation of follistatin gene expression in ameloblasts

Sp6 is a member of the Sp family of transcription factors that regulate a wide range of cellular functions, such as cell growth and differentiation. Sp6, also called epiprofin, is specifically expressed in tooth germ, limb bud, and hair follicle, but there is little information on its function. To investigate the possible role of Sp6 in tooth development, first we established an Sp6- overproducing clone, CHA9, and analyzed the features of the cell, including cell proliferation and gene expression. The parental cells of CHA9 are the ameloblast-lineage G5 cells that we previously established from rat dental epithelia of lower incisor. Sp6 overproduction accelerated cell proliferation and induced the expression of ameloblastin mRNA, a marker of ameloblast differentiation. Second, we performed genome-wide screening of Sp6 target genes by microarray analysis. Out of a total 20,450 genes, 448 genes were up-regulated and 500 genes were down-regulated by Sp6. We found the expression of follistatin, a BMP antagonist, to be 22.4-fold lower in CHA9 than in control cells. Transfection of the Sp6-antisense construct into CHA9 cells restored follistatin expression back to equivalent levels seen in control cells, indicating that Sp6 regulates follistatin gene expression in ameloblasts. Our findings demonstrate that the follistatin gene is one of the Sp6 target genes in ameloblasts and suggest that Sp6 promotes amelogenesis through inhibition of follistatin gene expression

Soluble matrix from osteoblastic cells induces mineralization by dental pulp cells

Dental pulp cells have a capacity to differentiate into mineralization-inducing cells. To clarify the molecular mechanism, we established an in vitro mineralization-inducing system by rat clonal dental pulp cell line, RPC-C2A, and tried to purify a mineralizationinducing factor in conditioned medium (CM) from preosteoblastic MC3T3-E1 cells. The active factor was impermeable to an ultrafiltrating membrane, and sedimented by ultracentrifugation. The sedimented factor was found as a needle-like structure about 1.3 μm in average length as observed by transmission electron microscopy. The factor contained type I collagen, suggesting not a matrix vesicle, but a soluble matrix. The mineralizationinducing activity was also detected in CM from primary culture of rat calvaria (RC) cells. These results suggested that the soluble matrices from osteoblastic cells serve, at least in part, as differentiation-inducing agents

Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism

Results from the Japan 2022 report card on physical activity for children and youth

Background/Objective: The 2020 Tokyo Olympics and Paralympic was held in 2021, although postponed due to the spread of COVID-19. This event might have an impact on physical activity (PA) of children and adolescents, but the national data on PA during the pandemic were not available. Therefore, the goal of the 2022 Japan Report Card on Physical Activity for Children and Youth (The 2022 Japan Report Card) is to assess and track levels of health behaviors related to PA, and health outcomes in Japanese children and adolescents, and environments and government strategy for PA just before the pandemic. Methods: The 2022 Japan Report Card consists of health behaviors and outcomes (8 indicators), and influences on health behaviors (4 indicators). Nationally representative data were used to score the indicators. Results: The key five health behaviors and outcomes (Overall PA: B −; Organized Sport: B −; Active Transportation: A −; Physical fitness: B, Weight status: A) were favorable. Sedentary Behavior and Sleep received C − and D − grades, respectively. Active Play could not be graded (INC). In the influences domain, Family and Peers was graded as C −, while School (B +), Community and Environment (B), and Government (B) were favorable. Conclusions: The 2022 Japan Report Card shows that Japanese children and adolescents had favorable levels of overall PA, active transportation to and from school, and weight status, and there was a generally favorable environment for PA and health, though sedentary behavior and sleep were unfavorable. Future nationally representative surveys on active play are needed

BMP2-induced gene profiling in dental epithelial cell line

Tooth development is regulated by epithelial-mesenchymal interactions and their reciprocal molecular signaling. Bone morphogenetic protein 2 (BMP2) is known as one of the inducers for tooth development. To analyze the molecular mechanisms of BMP2 on ameloblast differentiation (amelogenesis), we performed microarray analyses using rat dental epithelial cell line, HAT-7. After confirming that BMP2 could activate the canonical BMP-Smads signaling in HAT-7 cells, we analyzed the effects of BMP2 on 14,815 gene expressions and profiled them. Seventy-three genes were up-regulated and 28 genes were down-regulated by BMP2 treatment for 24 hours in HAT-7 cells. Functional classification revealed that 18% of up-regulated genes were ECM/adhesion molecules present in the enamel organ. Furthermore, we examined the expression of several differentiation markers in dental epithelial four cell-lineages including inner enamel epithelium (ameloblasts), stratum intermedium, stratum reticulum, and outer enamel epithelium. The results indicated that BMP2 might induce at least two different cell-lineage markers including a BMP antagonist expressed in HAT-7 cells, suggesting that BMP2 could accelerate amelogenesis via BMP signaling

Astrodynamics Science About Itokawa, Gravity and Ephemeris

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76347/1/AIAA-2006-6658-569.pd

Compliance with a physical activity guideline among junior high school students

Background: There were no nationwide moderate- to vigorous-intensity physical activity (MVPA) data relating to Japanese adolescents. This study assessed compliance with an MVPA guideline by adolescents, using a random sampling survey in Japan. The factors associated with compliance with the guideline were also examined. Methods: Participants were first- to third-grade Japanese junior high school students (307 boys and 255 girls). We analyzed data from the National Sports-Life Survey of Teens 2019, which used the Japanese version of physical activity (PA) questions in the World Health Organization Health Behavior in School-aged Children survey and potential correlates of MVPA. Results: Compliance with the PA guideline by the World Health Organization for Japanese students was 19.0% (95% confidence interval (CI), 15.8–22.3). The compliance of boys was significantly higher than that of girls (23.1%; 95% CI, 18.4–27.8; vs 14.1%; 95% CI, 9.8−18.4). The odds of meeting the PA guideline were significantly higher for boys in the second grade than boys in the first grade (odds ratio (OR) 1.78; 95% CI, 1.02–3.09), liking PA (for all: OR: 2.97; 95% CI, 1.32–6.69; for girls: OR: 2.99; 95% CI, 1.01–8.81), and sports participation (for all: OR: 4.77; 95% CI, 2.32–9.80; for boys: OR: 6.00; 95% CI, 1.81–19.89; for girls: OR: 4.08; 95% CI, 1.63–10.21). Conclusions: The results suggest that more than 80% of junior high school students were insufficiently physically active in Japan. Preferences for PA and sports participation may be important correlates of sufficient PA