Functional network of glycan-related molecules: Glyco-Net in Glycoconjugate Data Bank

<p>Abstract</p> <p>Background</p> <p>Glycans are involved in a wide range of biological process, and they play an essential role in functions such as cell differentiation, cell adhesion, pathogen-host recognition, toxin-receptor interactions, signal transduction, cancer metastasis, and immune responses. Elucidating pathways related to post-translational modifications (PTMs) such as glycosylation are of growing importance in post-genome science and technology. Graphical networks describing the relationships among glycan-related molecules, including genes, proteins, lipids and various biological events are considered extremely valuable and convenient tools for the systematic investigation of PTMs. However, there is no database which dynamically draws functional networks related to glycans.</p> <p>Description</p> <p>We have created a database called Glyco-Net <url>http://www.glycoconjugate.jp/functions/</url>, with many binary relationships among glycan-related molecules. Using search results, we can dynamically draw figures of the functional relationships among these components with nodes and arrows. A certain molecule or event corresponds to a node in the network figures, and the relationship between the molecule and the event are indicated by arrows. Since all components are treated equally, an arrow is also a node.</p> <p>Conclusions</p> <p>In this paper, we describe our new database, Glyco-Net, which is the first database to dynamically show networks of the functional profiles of glycan related molecules. The graphical networks will assist in the understanding of the role of the PTMs. In addition, since various kinds of bio-objects such as genes, proteins, and inhibitors are equally treated in Glyco-Net, we can obtain a large amount of information on the PTMs.</p

Synthesis of azulene-substituted benzofurans and isocoumarins via intramolecular cyclization of 1-ethynylazulenes, and their structural and optical properties

First published: 08 Dec 2017The preparation of azulene-substituted benzofurans and isocoumarins was established by two types of intramolecular cyclization reaction of 1-ethynylazulenes. 2-(1-Azulenyl)- and 2,3-bis(1-azulenyl)benzofurans were prepared by the palladium-catalyzed cross-coupling reaction of 1-iodoazulenes with 2-ethynylphenol and that of 1-ethynylazulenes with 2-iodophenol under Sonogashira-Hagihara reaction conditions following the intramolecular nucleophilic addition of the oxygen nucleophile to the presumed 1-arylethynylazulenes. In contrast, 1-(phenylethynyl)azulenes bearing an o-methoxycarbonyl function on the substituted phenyl moiety exhibited intramolecular cyclization either in the presence of trifluoroacetic acid or N-iodosuccinimide (NIS) to afford azulene-substituted isocoumarins and 4-iodoisocoumarins, and the structures were clarified by single-crystal X-ray analysis. The optical properties of these compounds were also investigated by UV/vis spectroscopy and theoretical calculations.ArticleORGANIC & BIOMOLECULAR CHEMISTRY. 16(3):480-489 (2018)journal articl

Reduced endogenous secretory RAGE in blood and bronchoalveolar lavage fluid is associated with poor prognosis in idiopathic pulmonary fibrosis

Background The endogenous secretory receptor for advanced glycation end products (esRAGE) is a soluble isoform produced by alternative splicing of the RAGE gene. The isoform has anti-inflammatory properties due to its inhibition of the RAGE/ligand interaction and is reduced in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the association of esRAGE serum and bronchoalveolar lavage fluid (BALF) levels with progression of IPF. Methods This study included 79 IPF patients and 90 healthy controls. IPF and control serum esRAGE levels were compared, and the correlation between serum and BALF esRAGE levels was analyzed in 57 IPF patient samples. We also investigated the relationship of esRAGE serum and BALF levels with prognoses and lung function parameters in patients with IPF. Results Serum esRAGE levels in IPF patients were significantly lower than those in healthy controls (162.0 +/- 102.4 ng/ml and 200.7 +/- 107.3 ng/ml,p = 0.009), although the baseline characteristics of age and smoking history were not matched. Serum levels of esRAGE were correlated with BALF esRAGE levels (r(s) = 0.317). The BALF esRAGE levels were also correlated with diffusion capacity for carbon monoxide (r(s) = 0.406). A Kaplan-Meier curve analysis and univariate/multivariate Cox hazard proportion analysis revealed that lower levels of esRAGE in blood and BALF were significantly associated with poorer prognoses in patients with IPF. Conclusions Decreased esRAGE levels in BALF and blood were associated with poor prognoses in patients with IPF. These results suggest that esRAGE could be related to the pathophysiology of IPF and serum esRAGE could be a potential prognostic marker of IPF.Peer reviewe

Endoplasmic Reticulum Associated Degradation of Spinocerebellar Ataxia-Related CD10 Cysteine Mutant

Spinocerebellar ataxia (SCA) is one of the most severe neurodegenerative diseases and is often associated with misfolded protein aggregates derived from the genetic mutation of related genes. Recently, mutations in CD10 such as C143Y have been identified as SCA type 43. CD10, also known as neprilysin or neuroendopeptidase, digests functional neuropeptides, such as amyloid beta, in the extracellular region. In this study, we explored the cellular behavior of CD10 C143Y to gain an insight into the functional relationship of the mutation and SCA pathology. We found that wild-type CD10 is expressed on the plasma membrane and exhibits endopeptidase activity in a cultured cell line. CD10 C143Y, however, forms a disulfide bond-mediated oligomer that does not appear by the wild-type CD10. Furthermore, the CD10 C143Y mutant was retained in the endoplasmic reticulum (ER) by the molecular chaperone BiP and was degraded through the ER-associated degradation (ERAD) process, in which representative ERAD factors including EDEM1, SEL1L, and Hrd1 participate in the degradation. Suppression of CD10 C143Y ERAD recovers intracellular transport but not enzymatic activity. Our results indicate that the C143Y mutation in CD10 negatively a ects protein maturation and results in ER retention and following ERAD. These findings provide beneficial insight into SCA type 43 pathology

Effect of Cys168 substitutions on the Thermostability and the Thermal Aggregation of Thermus thermophilus Inorganic Pyrophosphatase.

Thermus thermophilus Inorganic pyrophosphatase (Tth PPase) is comprised of homohexamer，and exhibits high thermostability. However，the thermal aggregation containing the cross-linked dimer was observed after heating above 85℃. Therefore，we focused on the sole cysteine (Cys168) in C-terminalregion，and evaluated the effects of substitutions at this position on thermostability and thermal aggregation of Tth PPase. Firstly，we prepared the four Cys168-substituted variants (C168A，L ，1，and F) by site-directed mutagenesis. Although all variants formed hexamer in native state，C168A variant exhibited the highest thermostabilities for the enzyme activity and quatemary structure in wild type and all variants，while the other variants decreased them drastically as the side chain at the 168 position was much more bulky and hydrophobic in Tth PPase. Moreover， suppression of thermal aggregation for C168A variant was observed in the ANS fluorescence experiments. Therefore，we suggest that the small volume and less hydrophobicity of side chain at 168 position may contribute to the conformational thermostability, and substitution with Ala is the most suitable for thermostabilization and suppression ofthermal aggregation of Tth PPase

Remarkable Dependence of the Final Charge Separation Efficiency on the Donor–Acceptor Interaction in Photoinduced Electron Transfer

The unprecedented dependence of final charge separation efficiency as a function of donor–acceptor interaction in covalently-linked molecules with a rectilinear rigid oligo-p-xylene bridge has been observed. Optimization of the donor–acceptor electronic coupling remarkably inhibits the undesirable rapid decay of the singlet charge-separated state to the ground state, yielding the final long-lived, triplet charge-separated state with circa 100% efficiency. This finding is extremely useful for the rational design of artificial photosynthesis and organic photovoltaic cells toward efficient solar energy conversion

Randomized, crossover questionnaire survey of acceptabilities of controlled-release mesalazine tablets and granules in ulcerative colitis patients

Background/Aims Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. Methods UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. Results A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). Conclusions CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication