Presynaptically Released Cbln1 Induces Dynamic Axonal Structural Changes by Interacting with GluD2 during Cerebellar Synapse Formation

SummaryDifferentiation of pre- and postsynaptic sites is coordinated by reciprocal interaction across synaptic clefts. At parallel fiber (PF)-Purkinje cell (PC) synapses, dendritic spines are autonomously formed without PF influence. However, little is known about how presynaptic structural changes are induced and how they lead to differentiation of mature synapses. Here, we show that Cbln1 released from PFs induces dynamic structural changes in PFs by a mechanism that depends on postsynaptic glutamate receptor delta2 (GluD2) and presynaptic neurexin (Nrx). Time-lapse imaging in organotypic culture and ultrastructural analyses in vivo revealed that Nrx-Cbln1-GluD2 signaling induces PF protrusions that often formed circular structures and encapsulated PC spines. Such structural changes in PFs were associated with the accumulation of synaptic vesicles and GluD2, leading to formation of mature synapses. Thus, PF protrusions triggered by Nrx-Cbln1-GluD2 signaling may promote bidirectional maturation of PF-PC synapses by a positive feedback mechanism

ギョウジ オヨビ ギョウジショク ニ カンス ル ニンチチョウサ

結果は、次の通りであった。(1)対象者の通園経験については、保育園が32%、幼稚園42%、両方が11%であった。(2)日本古来の食文化で非常に良いものと思うと答えたのが31%、教えていく必要が非常にあると思うは38%であった。(3)行事食を作ったことがあるかでは、「ある」が67%、どこで作ったかでは、「家」が89%、「園」が15%で、誰から教わったかでは「母」が75%、「祖母」が28%、「自分」が17%であった。(4)知っている年中行事について最も多かったのは、全体では「正月」、「ひなまつり」で、次いで、「節分」、「クリスマス」であった。食物栄養では、「正月」で90%、こども学は「ひなまつり」63%であり、専攻の特色が伺えた。(5)知っている行事食は、全体では、「お節料理」が多く、食物栄養88%、こども学62%、次いで、「雑煮」が食物栄養84%、こども学61%であった。また、作ったことがある行事食についても回答が多かったのは、「お節料理」と「雑煮」であった。(6)保育園で計画したい年中行事については、「クリスマス」が66%で最も多く、次いで、「ひなまつり」63%、「七夕まつり」60%、「節分」58%であった。We conducted the investigation into the event and the event food for 196 students of Suzuka junior college.The result is as follows.(1)About the school experience that students had been going to in the childhood. A nursery school was 32%, kindergarten was 42% and both of them were 11%.(2)About Japanese old and traditional food culture, 31% students answered that it is very good, and 38% students answered that it needs to teach it very much.(3)About cooking the event food that students had ever cooked before, 67% students had ever cooked before. And 89% students cooked in their house, 75%students had learned how to cook the event food from "mother", 28% students had learned from "a grandmother" and 17% students had learned it by oneself.(4)About the event that students knew the most, at the whole "New Year festival" and "the Doll\u27s festival]" were the most, and next to "The day before the official beginning of spring" and "Christmas". 90% students who majored in the Food and Nutrition were "New Year festival" and 63% students who majored in the Philosophy of Children were "the Doll\u27s festival". So we were able to ask you about the majoring characteristic.(5)About the event food that students knew the most, at the whole "New Year dishes" were the most. There were 88% students who majored in the Food and Nutrition and 62% students who majored in the Philosophy of Children. And next was "Soup containing vegetables and rice cakes for New Year festival", there were 84% students who majored in the Food and Nutrition, and 61% students who majored in the Philosophy of Children. In addition, it was "New Year dishes" and "Soup containing vegetable and rice cakes for New Year festival" that there were many answers from students had cooked it for the event food. (6)About the event food which it wanted to plan in a nursery, there was the most "Christmas" at 66%, next was "Doll\u27s festival" at 63%, and then "The before the official beginning of spring" at 58%

Impairments in Activities of Daily Living in Older Japanese Men in Hawaii and Japan

Introduction. Hypertension and cigarette smoking are dominant risk factors for cardiovascular disease in Japan while in westernized countries, broader effects encompass obesity, diabetes, and hypercholesterolemia. This paper examines whether different associations also appear important in the manifestation of activities of daily living (ADL) in older Japanese men in Hawaii and Japan. Methods. Measures of ADL (feeding, toileting, dressing, bathing, and walking around the house) were assessed from 1995 to 1999 in 1,893 men in Hawaii and 543 men in Japan. Concomitant risk factors were measured from 1990 to 1993. Results. In Hawaii, diabetes increased the odds of ≥1 ADL impairment nearly 1.5-fold (P = .020). A similar association was absent in Japan. In contrast, the odds of an ADL impairment in Japan was increased more than 5-fold in the presence of stroke (P < .001). The association in Hawaii was significantly weaker (P = .007). In both cohorts, past alcohol use was associated with a greater likelihood of ADL impairment. Conclusion. In this comparison of genetically similar samples, findings suggest that different strengths in risk factor associations with cardiovascular disease in Japan and westernized countries may also include different strengths in associations with impaired ADL

Differential responses of normal human coronary artery endothelial cells against multiple cytokines comparatively assessed by gene expression profiles

AbstractEndothelial cells play an important role in terms of biological functions by responding to a variety of stimuli in the blood. However, little is known about the molecular mechanism involved in rendering the variety in the cellular response. To investigate the variety of the cellular responses against exogenous stimuli at the gene expression level, we attempted to describe the cellular responses with comprehensive gene expression profiles, dissect them into multiple response patterns, and characterize the response patterns according to the information accumulated so far on the genes included in the patterns. We comparatively analyzed in parallel the gene expression profiles obtained with DNA microarrays from normal human coronary artery endothelial cells (HCAECs) stimulated with multiple cytokines, interleukin-1β, tumor necrosis factor-α, interferon-β, interferon-γ, and oncostatin M, which are profoundly involved in various functional responses of endothelial cells. These analyses revealed that the cellular responses of HCAECs against these cytokines included at least 15 response patterns specific to a single cytokine or common to multiple cytokines. Moreover, we statistically extracted genes contained within the individual response patterns and characterized the response patterns with the genes referring to the previously accumulated findings including the biological process defined by the Gene Ontology Consortium (GO). Out of the 15 response patterns in which at least one gene was successfully extracted through the statistical approach, 11 response patterns were differentially characterized by representing the number of genes contained in individual criteria of the biological process in the GO only. The approach to dissect cellular responses into response patterns and to characterize the pattern at the gene expression level may contribute to the gaining of insight for untangling the diversity of cellular functions

Effect of triclocarban on membrane potential of rat thymocytes : Assessment with bis-(1,3-dibutylbarbituric acid)trimethine oxonol

The effect of triclocarban (TCC), an　environmental pollutant from household items and health care products, on membrane potential of rat thymocytes was examined by a flow cytometry with a fluorescent probe sensitive to membrane potential, bis-(1,3-dibutylbarbituric acid)trimethine oxonol, because TCC changes intracellular ionic circumstance that may affect the membrane potential. TCC at 0.3 μM or more (up to 3 μM) depolarized the membranes. This TCC-induced phenomenon was against our prediction because TCC increases intracellular Ca2+ concentration that activates Ca2+-dependent K+ channels, resulting in a hyperpolarization. The depolarization was still observed under Ca2+-free condition, but not under Na+-free condition. Furthermore, TCC hyperpolarized the membranes under Ca2+- and Na+-free condition. To see if TCC inhibits Ca2+-dependent hyperpolarization, the effect of A23187, a calcium ionophore, on the membrane potential was examined in the cells treated with TCC. A23187 induced large depolarization in the cells treated with 0.3–3 μM TCC. The A23187-induced depolarization in the presence of TCC was greatly attenuated under Na+-free or Ca2+-free condition whereas A23187 elicited hyperpolarization in the cells treated with 0.3–3 μM TCC under Ca2+- and Na+-free condition. Results suggest that 0.3–3 μM TCC increases membrane permeability of Na+ and Ca2+, resulting in the depolarization. Large depolarization induced by TCC in the presence of external Ca2+ and Na+ may mask the hyperpolarization elicited via the increase in intracellular Ca2+ concentration by TCC. Thus, there is a possibility that TCC depolarizes membranes of lymphocytes, resulting in alteration of cellular functions of lymphocytes

Epoprostenol sodium for treatment of pulmonary arterial hypertension

　The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required

Control of Diabetes Mellitus and Long-Term Prognosis in Stroke Patients: The Shiga Stroke and Heart Attack Registry

BACKGROUND: The relationship between diabetes control status and long-term prognosis after stroke incidence remains unclear. This study aimed to investigate the effect of diabetes status at admission on long-term survival in patients with first-ever stroke. METHODS: A retrospective cohort study was conducted based on the Shiga Stroke and Heart Attack Registry in Japan. Patients were classified according to their diabetes status and glycated hemoglobin (HbA1c) value at hospital admission into the following: (1) free of diabetes (no history of diabetes and HbA1c <6.5%); (2) good control (history of diabetes and HbA1c <7%; free of history and 6.5% ≤HbA1c <7%); and (3) poor control (with or without a history of diabetes and HbA1c ≥7%). Multivariable Cox regression models were used to evaluate the association between diabetes status and long-term survival from stroke onset. Additionally, we also evaluated the association between diabetes status and conditional survival, beginning 29 days after stroke onset. RESULTS: A total of 6, 331 first-ever stroke patients were eligible for this study. Among study patients, the mean (±SD) age was 72.85 ± 13.19 years, and the mean (±SD) follow-up year was 2.76 ± 1.66 years; additionally, 42.09% of patients were women. Among patients with all strokes, considering the free-of-diabetes group as the reference group, the adjusted hazard ratio (95% confidence interval) for mortality was 1.26 (1.10, 1.44) in the good control group and 1.22 (1.05, 1.41) in the poor control group. Among patients with ischemic stroke, the adjusted hazard ratio was 1.24 (1.06, 1.46) in good control group and 1.27 (1.08, 1.50) in poor control group. After excluding patients who died within 28 days, the adjusted hazard ratio for conditional mortality in the poor control group was 1.31 (1.12, 1.54) among all stroke patients and 1.29 (1.08, 1.54) among ischemic stroke patients. No significant associations were observed between diabetic status and long-term mortality in intracerebral hemorrhage patients. CONCLUSIONS: The findings suggest that first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control

A series of ENU-induced single-base substitutions in a long-range cis-element altering Sonic hedgehog expression in the developing mouse limb bud

AbstractMammal–fish-conserved-sequence 1 (MFCS1) is a highly conserved sequence that acts as a limb-specific cis-acting regulator of Sonic hedgehog (Shh) expression, residing 1 Mb away from the Shh coding sequence in mouse. Using gene-driven screening of an ENU-mutagenized mouse archive, we obtained mice with three new point mutations in MFCS1: M101116, M101117, and M101192. Phenotype analysis revealed that M101116 mice exhibit preaxial polydactyly and ectopic Shh expression at the anterior margin of the limb buds like a previously identified mutant, M100081. In contrast, M101117 and M101192 show no marked abnormalities in limb morphology. Furthermore, transgenic analysis revealed that the M101116 and M100081 sequences drive ectopic reporter gene expression at the anterior margin of the limb bud, in addition to the normal posterior expression. Such ectopic expression was not observed in the embryos carrying a reporter transgene driven by M101117. These results suggest that M101116 and M100081 affect the negative regulatory activity of MFCS1, which suppresses anterior Shh expression in developing limb buds. Thus, this study shows that gene-driven screening for ENU-induced mutations is an effective approach for exploring the function of conserved, noncoding sequences and potential cis-regulatory elements

ギョギョウシュウラク ニ オケル ギョウジショク ノ ジゾク ト ヘンヨウ

今回の調査によって、奈屋浦において現在でも精霊棚(餓鬼棚)の慣習が残っていることが確認され、さらに供えられる料理や食物の内容の詳細を明らかにすることができた。奈屋浦で精霊棚(餓鬼棚)の伝統的な姿が残ったのは、次に示す3点に下支えされていることが要因であると考える。1)集落人口が維持されたこと(伝統を継承する若年層が一定数確保された)2)生業構造(漁業人口)が維持されたこと(類似した生活構造にある人々が多い)3)地域住民のつながりが深いこと(精霊棚に供える野菜などを分け合ってまかなっている)This paper examines continuance and transformation of meals of traditional event in fishing community. Specially, it investigates how Gakidana, special meal for the spirits of ancestors in Bon period, has been changed and maintained in Nayaura, a fishing village located in southern Mie prefecture. By meticulous research into traditional meals and literature study on socioeconomic background of this village, the study reveals three factors that have maintained the custom of traditional meals:1) Maintenance of population supported by economic development has produced flame keepers.2) Maintenance of population of fishery industry has given inhabitants similar life structure.3) Close relationship among inhabitants results in sharing ingredients for traditional meals