Kyushu University

About: Kyushu University is a education organization based out in Fukuoka, Japan. It is known for research contribution in the topics: Population & Catalysis. The organization has 68284 authors who have published 135190 publications receiving 3055928 citations. The organization is also known as: Kyūshū Daigaku.

Structure of the human histamine H1 receptor complex with doxepin.

Abstract: The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H1 receptor (H1R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H1R complex with doxepin, a first-generation H1R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp 4286.48, a highly conserved key residue in G-protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H1R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys 1915.39 and/or Lys 179ECL2, both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H1R antagonist specificity against H1R. The common antihistamines are antagonists of histamine H1 receptor (H1R), a G-protein-coupled receptor (GPCR) that is expressed in various tissues including airway, intestinal smooth muscle and brain. The X-ray crystal structure of human H1R in the presence of doxepin, a first-generation H1R antagonist, is now reported. It shows that the drug resides in a much deeper pocket than in other aminergic GPCR structures. Analysis of drug–protein interactions should facilitate the development of antihistamines that are more selective and less likely to cause side effects than those currently available.

Efficient Activation of Aromatic C-H Bonds for Addition to C-C Multiple Bonds

Abstract: Efficient electrophilic metalation of aromatic C-H bonds leading to new C-C bond formation through regio- and stereoselective addition to alkynes and alkenes has been realized by a catalytic amount (0.02 to 5 mole percent) of palladium(II) or platinum(II) compounds in a mixed solvent containing trifluoroacetic acid at room temperature. Various arenes undergo unexpected selective trans hydroarylation to terminal or internal CcC bonds inter- and intramolecularly with high efficiency (up to a turnover number of 4500 for palladium), especially for electron-rich arenes, giving thermodynamically unfavorable cis-alkenes, and the oxygen- and nitrogen-containing heterocycles. The simplicity, generality, and efficiency of this process should be very attractive to the possible industrial application for the functionalization of arenes.

Design of metal-complex magnets. Syntheses and magnetic properties of mixed-metal assemblies {NBu4[MCr(ox)3]}x (NBu4+ = tetra(n-butyl)ammonium ion; ox2- = oxalate ion; M = Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+)

Abstract: The reaction of K 3 [Cr(ox) 3 ].3H 2 O, a metal(II) salt, and tetra(n-butyl)ammonium bromide in the molar ratio of 1:1:1.5 in water at room temperature afforded a series of mixed-metal assemblies with the formula {NBu 4 [MCr(ox) 3 ]} x (M=Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ ).

The evolution of costly mate preferences ii. the "handicap" principle.

Abstract: We use a general additive quantitative genetic model to study the evolution of costly female mate choice by the "handicap" principle. Two necessary conditions must be satisfied for costly preference to evolve. The conditions are (i) biased mutation pressure on viability and (ii) a direct relationship between the degree of expression of the male mating character and viability. These two conditions explain the success and failure of previous models of the "handicap" principle. Our model also applies to other sources of fitness variation like migration and host-parasite coevolution, which cause effects equivalent to biased mutation.

International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease

Abstract: A. Khosroshahi, Z. S. Wallace, J. L. Crowe, T. Akamizu, A. Azumi, M. N. Carruthers, S. T. Chari, E. Della-Torre, L. Frulloni, H. Goto, P. A. Hart, T. Kamisawa, S. Kawa, M. Kawano, M. H. Kim, Y. Kodama, K. Kubota, M. M. Lerch, M. L€ ohr, Y. Masaki, S. Matsui, T. Mimori, S. Nakamura, T. Nakazawa, H. Ohara, K. Okazaki, J. H. Ryu, T. Saeki, N. Schleinitz, A. Shimatsu, T. Shimosegawa, H. Takahashi, M. Takahira, A. Tanaka, M. Topazian, H. Umehara, G. J. Webster, T. E. Witzig, M. Yamamoto, W. Zhang, T. Chiba, and J. H. Stone