Calreticulin and integrin alpha dissociation induces anti-inflammatory programming in animal models of inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils. Transcriptome analysis on colon samples from dextran sodium sulfate-induced colitis mice reveals that the increased expression of pro-inflammatory genes is downregulated by ER-464195-01. Its prophylactic and therapeutic administration to IBD mouse models ameliorates the severity of their diseases. We propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of IBD

ON THE OCEANOGRAPHIC CONDITIONS IN THE ATLANTIC AND INDIAN SOUTHERN WATERS

Based on the data obtained by the UMITAKA-MARU (Tokyo Univ. of Fisheries, 1453) during the period from Dec. 1961 to Feb. 1962, the general oceanographic conditions are discussed in this paper. During this expedition the temperature, salinity, dissolved oxygen, PH, Phosphate-P and Silicate-Si are investigated at all stations. As a result the followings are summarized; (1) along the oceanographic sections off Australia and Africa the Antarctic Convergences are clearly distinguished, (2) in the Indian Antarctic waters the south-going warm deep water affects to the higher latitudes zone than in the Atlantic region, (3) in the Weddell cold water region where the northerly and southerly oceanographic sections are investigated the upwelling of Warm Deep Water is critically observed, (4) by the chart of dynamical topography the meandering of west-wind drift current around the Weddell cold water region is estimated

Characterization of an Exo-β-1,3-Galactanase from Clostridium thermocellum

A gene encoding an exo-β-1,3-galactanase from Clostridium thermocellum, Ct1,3Gal43A, was isolated. The sequence has similarity with an exo-β-1,3-galactanase of Phanerochaete chrysosporium (Pc1,3Gal43A). The gene encodes a modular protein consisting of an N-terminal glycoside hydrolase family 43 (GH43) module, a family 13 carbohydrate-binding module (CBM13), and a C-terminal dockerin domain. The gene corresponding to the GH43 module was expressed in Escherichia coli, and the gene product was characterized. The recombinant enzyme shows optimal activity at pH 6.0 and 50°C and catalyzes hydrolysis only of β-1,3-linked galactosyl oligosaccharides and polysaccharides. High-performance liquid chromatography analysis of the hydrolysis products demonstrated that the enzyme produces galactose from β-1,3-galactan in an exo-acting manner. When the enzyme acted on arabinogalactan proteins (AGPs), the enzyme produced oligosaccharides together with galactose, suggesting that the enzyme is able to accommodate a β-1,6-linked galactosyl side chain. The substrate specificity of the enzyme is very similar to that of Pc1,3Gal43A, suggesting that the enzyme is an exo-β-1,3-galactanase. Affinity gel electrophoresis of the C-terminal CBM13 did not show any affinity for polysaccharides, including β-1,3-galactan. However, frontal affinity chromatography for the CBM13 indicated that the CBM13 specifically interacts with oligosaccharides containing a β-1,3-galactobiose, β-1,4-galactosyl glucose, or β-1,4-galactosyl N-acetylglucosaminide moiety at the nonreducing end. Interestingly, CBM13 in the C terminus of Ct1,3Gal43A appeared to interfere with the enzyme activity toward β-1,3-galactan and α-l-arabinofuranosidase-treated AGP

Concise Synthesis of 2-Benzazepine Derivatives and Their Biological Activity

2-Benzazepines, which are potentially good candidates for new drug therapies to treat skin wounds, were readily prepared from substituted cinnamylamide via an intramolecular Friedel–Crafts reaction. With few steps and effective reactions, the procedure enables a rapid derivatization of 2-benzazepines. Moreover, optically active 4-substituted-2-benzazepines were prepared from chiral α-substituted cinnamylamides, which were readily prepared by asymmetric α-alkylation of chiral cinnamyl oxazolidinone amides. We have easily prepared a library of more than 20 derivatives and examined the biological activity of the compounds