Pentagram Map by Euclidean Approach

As one type of incidence theory, the geometry of pentagram map seems quite classical at first. However, this is an excellent example of such a classical idea developed into a marvellous insight by some modern approach. We introduce an alternative approach based on the setting of the ordinary Euclidean geometry.Comment: 10 pages, 4 figure

Nesfatin-1 evokes Ca2+ signaling in isolated vagal afferent neurons via Ca2+ influx through N-type channels

金沢大学医薬保健研究域医学系Nesfatin-1, processed from nucleobindin 2, is an anorexigenic peptide expressed in the brain and several peripheral tissues including the stomach and pancreas. Peripheral, as well as intracerebroventricular, administration of nesfatin-1 suppresses feeding behavior, though underlying mechanisms are unknown. In this study, we examined effects of nesfatin-1 on cytosolic Ca2+ concentration ([Ca2+]i) in the neurons isolated from the vagal afferent nodose ganglion of mice. Nesfatin-1 at 10-10-10-8 M increased [Ca2+]i in the isolated neurons in a concentration-dependent manner, and at 10-8 M it increased [Ca2+]i in 33 out of 263 (12.5%) neurons. These responses were inhibited under Ca2+-free conditions and by N-type Ca2+ channel blocker, ω-conotoxin GVIA. All the nesfatin-1-responsive neurons also exhibited [Ca2+]i responses to capsaicin and cholecystokinin-8. These results provide direct evidence that nesfatin-1 activates vagal afferent neurons by stimulating Ca2+ influx through N-type channels, demonstrating the machinery through which peripheral nesfatin-1 can convey signals to the brain. © 2009 Elsevier Inc. All rights reserved

A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia

Cofilin mediates lamellipodium extension and polarized cell migration by stimulating actin filament dynamics at the leading edge of migrating cells. Cofilin is inactivated by phosphorylation at Ser-3 and reactivated by cofilin-phosphatase Slingshot-1L (SSH1L). Little is known of signaling mechanisms of cofilin activation and how this activation is spatially regulated. Here, we show that cofilin-phosphatase activity of SSH1L increases ∼10-fold by association with actin filaments, which indicates that actin assembly at the leading edge per se triggers local activation of SSH1L and thereby stimulates cofilin-mediated actin turnover in lamellipodia. We also provide evidence that 14-3-3 proteins inhibit SSH1L activity, dependent on the phosphorylation of Ser-937 and Ser-978 of SSH1L. Stimulation of cells with neuregulin-1β induced Ser-978 dephosphorylation, translocation of SSH1L onto F-actin–rich lamellipodia, and cofilin dephosphorylation. These findings suggest that SSH1L is locally activated by translocation to and association with F-actin in lamellipodia in response to neuregulin-1β and 14-3-3 proteins negatively regulate SSH1L activity by sequestering it in the cytoplasm

Nesfatin-1 suppresses peripheral arterial remodeling without elevating blood pressure in mice

Nesfatin-1 is a novel anorexic peptide hormone that also exerts cardiovascular protective effects in rodent models. However, nesfatin-1 treatment at high doses also exerts vasopressor effects, which potentially limits its therapeutic application. Here, we evaluated the vasoprotective and vasopressor effects of nesfatin -1 at different doses in mouse models. Wild-type mice and those with the transgene nucleobindin-2, a precursor of nesfatin-1, were employed. Wild-type mice were randomly assigned to treatment with vehicle or nesfatin-1 at 0.2, 2.0 or 10 μg/kg/day (Nes-0.2, Nes-2, Nes-10, respectively). Subsequently, mice underwent femoral artery wire injury to induce arterial remodeling. After 4 weeks, injured arteries were collected for morphometric analysis. Compared with vehicle, nesfatin-1 treatments at 2.0 and 10 μg/kg/day decreased body weights and elevated plasma nesfatin-1 levels with no changes in systolic blood pressure. Furthermore, these treatments reduced neointimal hyperplasia without inducing undesirable remodeling in injured arteries. However, nesfatin-1 treatment at 0.2 μg/kg/day was insufficient to elevate plasma nesfatin-1 levels and showed no vascular effects. In nucleobindin-2- transgenic mice, blood pressure was slightly higher but neointimal area was lower than those observed in littermate controls. In cultured human vascular endothelial cells, nesfatin-1 concentration-dependently increased nitric oxide production. Additionally, nesfatin-1 increased AMP-activated protein kinase phosphorylation, which was abolished by inhibiting liver kinase B1. We thus demonstrated that nesfatin-1 treatment at appropriate doses suppressed arterial remodeling without affecting blood pressure. Our findings indicate that nesfatin-1 can be a therapeutic target for improved treatment of peripheral artery disease

Combination Therapy with a Sodium-Glucose Cotransporter 2 Inhibitor and a Dipeptidyl Peptidase-4 Inhibitor Additively Suppresses Macrophage Foam Cell Formation and Atherosclerosis in Diabetic Mice

Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day), either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe−/−) mice. Ipragliflozin and alogliptin monotherapies improved glucose intolerance; however, combination therapy did not show further improvement. The foam cell formation of peritoneal macrophages was suppressed by both the ipragliflozin and alogliptin monotherapies and was further enhanced by combination therapy. Although foam cell formation was closely associated with HbA1c levels in all groups, DPP-4i alone or the combination group showed further suppression of foam cell formation compared with the control or SGLT2i group at corresponding HbA1c levels. Both ipragliflozin and alogliptin monotherapies decreased scavenger receptors and increased cholesterol efflux regulatory genes in peritoneal macrophages, and combination therapy showed additive changes. In diabetic Apoe−/− mice, combination therapy showed the greatest suppression of plaque volume in the aortic root. In conclusion, combination therapy with SGLT2i and DPP4i synergistically suppresses macrophage foam cell formation and atherosclerosis in diabetic mice

Involvement of Vascular Endothelial Cells in the Anti-atherogenic Effects of Liraglutide in Diabetic Apolipoprotein E-null Mice

Glucagon-like peptide 1 receptor agonists （GLP-1RAs） have been shown to exert anti-atherosclerotic effects via multiple mechanisms on different types of cells. However, it is unclear which of these mechanisms are crucial. We investigated the role of vascular endothelial cells （VECs） in the anti-atherogenic effects of the GLP-1RA liraglutide in a mouse model of atherosclerosis. Streptozotocin-induced diabetic apolipoprotein E-null mice were randomly assigned to treatment with either vehicle （saline） or liraglutide （107nmol/kg/day）, and were subjected to femoral artery wire injury to remove VECs. After 4 weeks, vessel samples were collected for analysis. Streptozotocin-injected mice had fasting plasma glucose levels of ＞300mg/dl and hemoglobin A1c levels of ＞9％, indicating that the injections had induced severe hyperglycemia. However, there were no differences in metabolic characteristics such as levels of hemoglobin A1c, fasting plasma glucose, total cholesterol, and triglycerides between the vehicle and liraglutide groups. Analysis of atherosclerotic plaque formation revealed that liraglutide treatment significantly suppressed plaque formation in the aorta. In addition, liraglutide treatment reduced plaque volume and intra-plaque macrophage accumulation at the aortic sinus. Furthermore, liraglutide treatment suppressed vascular expression of pro-inflammatory cytokines. In uninjured femoral arteries, no plaques were observed; however, severe plaque formation occurred in femoral arteries that had been injured by wire insertion to remove VECs. Unlike in the uninjured aorta, liraglutide treatment did not affect plaque volume or arterial remodeling （intimal and medial thinning, and arterial dilation） in wire-injured femoral arteries. Of the various cells that liraglutide affects, VECs play a central role in liraglutide’s anti-atherogenic effects in diabetic mice

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study

Purpose: The effects of daily teriparatide (20 μg) (D-PTH), weekly high-dose teriparatide (56.5 μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients.Methods: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months\u27 treatment compared with baseline.Results: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (− 4.1%, − 3.0%, − 1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (− 1.8%, − 0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (− 0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (− 0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%).Conclusions: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH

コバヤシ タケシ ト ニホン ノ インタープリテーション

Professor Takeshi Kobayashi was a leading and representative figure in interpretation of Japan. He passed awaysuddenly on March 13th in 2013 at the age of 55. This paper describes a brief history of interpretation in Japan, following thesteps that Professor Kobayashi had taken in the field of interpretation and environmental education. Professor Kobayashistarted his interpretation career at the Takao Visitor Center as a ranger of the Nature Conservation Society of Japan in 1983.He established the Center for Environmental Studies in order to focus on nature interpretation in 1988. He had also coordinatedthe Japan-U.S. Interpreter Training Seminar, which was jointly supported by the U.S. National Park Services, since 1995 anddeveloped a number of other interpreter training programs in Japan. He played a central role in those training courses in 1990s and 2000s of Japan, during which the Ministry of the Environment and the Ministry of Education, Culture, Sports,Science and Technology were active in offering training for interpreters and outdoor educators. He became a professor at theGifu Academy of Forest Science and Culture in 2005 and a professor at the Department of Animal Sciences, the Faculty ofLife and Environmental Sciences, Teikyo University of Science in 2010. He developed courses for instructors and trainers ofenvironmental education and interpretation. Professor Kobayashi helped offering opportunities for domestic and internationalinterpreters to meet and to develop network. He had been engaged in developing interpretation through projects and events,human resource development, and networking, and greatly contributed to the enhancement of interpretation in Japan till thelast day