1,7-Diethyl-4,10-diisopropyl­tetra­cene

The mol­ecule of the title compound, C28H32, is located on a crystallographic inversion center. The ethyl groups are essentially coplanar with the tetra­cene ring, making a torsion angle of −0.4 (4)°. The isopropyl groups adopt an asymmetric conformation with their terminal methyl groups positioned on opposite sides of the tetra­cene plane [the Me—C—C—C torsion angles are −22.5 (4) and 100.9 (3)°]. In the crystal, the mol­ecules adopt an arrangement without significant π–π inter­actions along the stacking direction (y axis)

LTP induction within a narrow critical period of immature stages enhances the survival of newly generated neurons in the adult rat dentate gyrus

Neurogenesis occurs in the adult hippocampus of various animal species. A substantial fraction of newly generated neurons die before they mature, and the survival rate of new neurons are regulated in an experience-dependent manner. Previous study showed that high-frequency stimulation (HFS) of perforant path fibers to the hippocampal dentate gyrus (DG) induces the long-term potentiation (LTP) in the DG, and enhances the survival of newly generated neurons in the DG. In this study, we addressed whether a time period exists during which the survival of new neurons is maximally sensitive to the HFS. We found that the enhancement of cell survival by HFS was exclusively restricted to the specific narrow period during immature stages of new neurons (7-10 days after birth). Furthermore, the pharmacological blockade of LTP induction suppressed the enhancement of cell survival by the HFS. These results suggest that the LTP induction within a narrow critical period of immature stages enhances the survival of newly generated neurons in rat DG

The Practice of Basic Informatics 2020

Version 2020/04/02Kyoto University provides courses on 'The Practice of Basic Informatics' as part of its Liberal Arts and Sciences Program. The course is taught at many schools and departments, and course contents vary to meet the requirements of these schools and departments. This textbook is made open to the students of all schools that teach these courses. As stated in Chapter 1, this book is written with the aim of building ICT skills for study at university, that is, ICT skills for academic activities. Some topics may not be taught in class. However, the book is written for self-study by students. We include many exercises in this textbook so that instructors can select some of them for their classes, to accompany their teaching plans. The courses are given at the computer laboratories of the university, and the contents of this textbook assume that Windows 10 and Microsoft Office 2016 are available in these laboratories. In Chapter 13, we include an introduction to computer programming; we chose Python as the programming language because on the one hand it is easy for beginners to learn, and on the other, it is widely used in academic research. To check the progress of students' self-study, we have attached assessment criteria (a 'rubric') of this course as an Appendix. Current ICT is a product of the endeavors of many people. The "Great Idea" columns are included to show appreciation for such work. Dr. Yumi Kitamura and Dr. Hirohisa Hioki wrote Chapters 4 and 13, respectively. The remaining chapters were written by Dr. Hajime Kita. In revision for 2018 edition and after, Dr. Hiroyuki Sakai has participated in the author group, and Dr. Donghui Lin has also joined for English edition 2019. The authors hope that this textbook helps you to improve your academic ICT skill set. The content included in this book is selected based on the reference course plan discussed in the course development team for informatics at the Institute for Liberal Arts and Sciences. In writing this textbook, we obtained advice and suggestions from staffs of the Network Section, Information Infrastructure Division, Department of Planning and Information Management Department, Kyoto University on Chapters 2 and 3, from Mr. Sosuke Suzuki, NTT Communications Corporation also on Chapter 3, Rumi Haratake, Machiko Sakurai and Taku Sakamoto of the User Support Division, Kyoto University Library on Chapter 4. Dr. Masako Okamoto of Center for the Promotion of Excellence in Higher Education, Kyoto University helped us in revision of 2018 Japanese Edition. The authors would like to express their sincere gratitude to the people who supported them

Betuletol, a Propolis Component, Suppresses IL-33 Gene Expression and Effective against Eosinophilia

Propolis, a resinous substance produced by honeybees, has been used in folk medicine since ancient times due to its many biological benefits such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects. Propolis contains flavonoids, terpenoids, aromatic aldehydes, and alcohols, which vary with different climate and environmental conditions. In our study, we examined the antiallergic activity of Brazilian green propolis (BGP) and isolated the active compound that can suppress an allergy-sensitive gene, IL-33, expression and eosinophilia. Ethanolic extract of BGP freeze-dried powder was fractionated with several solvent systems, and the active fractions were collected based on activity measurement. The single active compound was found by thin-layer chromatography. Using column chromatography and NMR, the active compound was isolated and identified as 3,5,7-trihydroxy-6,4’-dimethoxyflavone, also known as betuletol. Further, the antiallergic activity of that has been examined in PMA-induced up-regulation of IL-33 gene expression in Swiss 3T3 cells. Our data showed the IL-33 gene suppression both by BGP and the isolated active compound, betuletol. We also found that betuletol suppressed ERK phosphorylation, suggesting it could be effective in suppressing IL-33 mediated eosinophilic chronic inflammation and will provide new insights to develop potent therapeutics against allergic inflammations

LPS 刺激ヒト歯肉線維芽細胞におけるExtracellular Signal-Regulated Kinase のリン酸化抑制を介した葛根湯の炎症反応抑制効果

Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. The chemical mediator prostaglandin E2 (PGE2) and cytokines such as interleukin- (IL-)6 and IL-8 have been known to play important roles in inflammatory responses and tissue degradation. In the present study, we investigated the effects of a kampo medicine, kakkonto (TJ-1), on the production of prostaglandin E2 (PGE2), IL-6, and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Kakkonto concentration dependently suppressed LPS-induced PGE2 production but did not alter basal PGE2 levels. In contrast, kakkonto significantly increased LPSinduced IL-6 and IL-8 production. Kakkonto decreased cyclooxygenase- (COX-)1 activity to approximately 70% at 1mg/mL but did not affect COX-2 activity. Kakkonto did not affect cytoplasmic phospholipase A2 (cPLA2), annexin1, or LPS-induced COX-2 expression. Kakkonto suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA2 phosphorylation. These results suggest that kakkonto decreased PGE2 production by inhibition of ERK phosphorylation which leads to inhibition of cPLA2 phosphorylation and its activation. Therefore, kakkonto may be useful to improve gingival inflammation in periodontal disease.2014博士（歯学）松本歯科大

Diabetes-Related Ankyrin Repeat Protein (DARP/Ankrd23) Modifies Glucose Homeostasis by Modulating AMPK Activity in Skeletal Muscle.

Skeletal muscle is the major site for glucose disposal, the impairment of which closely associates with the glucose intolerance in diabetic patients. Diabetes-related ankyrin repeat protein (DARP/Ankrd23) is a member of muscle ankyrin repeat proteins, whose expression is enhanced in the skeletal muscle under diabetic conditions; however, its role in energy metabolism remains poorly understood. Here we report a novel role of DARP in the regulation of glucose homeostasis through modulating AMP-activated protein kinase (AMPK) activity. DARP is highly preferentially expressed in skeletal muscle, and its expression was substantially upregulated during myotube differentiation of C2C12 myoblasts. Interestingly, DARP-/- mice demonstrated better glucose tolerance despite similar body weight, while their insulin sensitivity did not differ from that in wildtype mice. We found that phosphorylation of AMPK, which mediates insulin-independent glucose uptake, in skeletal muscle was significantly enhanced in DARP-/- mice compared to that in wildtype mice. Gene silencing of DARP in C2C12 myotubes enhanced AMPK phosphorylation, whereas overexpression of DARP in C2C12 myoblasts reduced it. Moreover, DARP-silencing increased glucose uptake and oxidation in myotubes, which was abrogated by the treatment with AICAR, an AMPK activator. Of note, improved glucose tolerance in DARP-/- mice was abolished when mice were treated with AICAR. Mechanistically, gene silencing of DARP enhanced protein expression of LKB1 that is a major upstream kinase for AMPK in myotubes in vitro and the skeletal muscle in vivo. Together with the altered expression under diabetic conditions, our data strongly suggest that DARP plays an important role in the regulation of glucose homeostasis under physiological and pathological conditions, and thus DARP is a new therapeutic target for the treatment of diabetes mellitus

Role of Semaphorin 3A in Kidney Development and Diseases

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is a secreted and membrane-associated protein, which regulates diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence has revealed that excess SEMA3A expression and the subsequent signaling pathway aggravate kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports have demonstrated that the inhibition of SEMA3A ameliorated kidney injury via a reduction in cell apoptosis, fibrosis and inflammation; thus, SEMA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized the current knowledge regarding the role of SEMA3A in kidney pathophysiology and their potential use in kidney diseases