SIDD: A Semantically Integrated Database towards a Global View of Human Disease

Background

A number of databases have been developed to collect disease-related molecular, phenotypic and environmental features (DR-MPEs), such as genes, non-coding RNAs, genetic variations, drugs, phenotypes and environmental factors. However, each of current databases focused on only one or two DR-MPEs. There is an urgent demand to develop an integrated database, which can establish semantic associations among disease-related databases and link them to provide a global view of human disease at the biological level. This database, once developed, will facilitate researchers to query various DR-MPEs through disease, and investigate disease mechanisms from different types of data.

Methodology

To establish an integrated disease-associated database, disease vocabularies used in different databases are mapped to Disease Ontology (DO) through semantic match. 4,284 and 4,186 disease terms from Medical Subject Headings (MeSH) and Online Mendelian Inheritance in Man (OMIM) respectively are mapped to DO. Then, the relationships between DR-MPEs and diseases are extracted and merged from different source databases for reducing the data redundancy.

Conclusions

A semantically integrated disease-associated database (SIDD) is developed, which integrates 18 disease-associated databases, for researchers to browse multiple types of DR-MPEs in a view. A web interface allows easy navigation for querying information through browsing a disease ontology tree or searching a disease term. Furthermore, a network visualization tool using Cytoscape Web plugin has been implemented in SIDD. It enhances the SIDD usage when viewing the relationships between diseases and DR-MPEs. The current version of SIDD (Jul 2013) documents 4,465,131 entries relating to 139,365 DR-MPEs, and to 3,824 human diseases. The database can be freely accessed from: http://mlg.hit.edu.cn/SIDD.     

Flavone and isoflavone derivatives of terrestrial plants as larval settlement inhibitors of the barnacle Balanus amphitrite

To determine whether they could serve as non-toxic or less damaging alternative antifouling (AF) agents, 17 flavone and isoflavone derivatives were isolated from terrestrial plant extracts, purified and examined for their ability to inhibit the settlement of barnacle (Balanus amphitrite) cyprids. In larval bioassays, eight compounds showed strong anti-larval settlement activities, with EC(50) values <10 microg ml(-1). Through an analysis of the structure-activity relationship of these compounds, it was found that (1) the structural difference between flavones and isoflavones did not affect their AF activities; (2) the 5-hydroxyl group on the skeletons played a key role in AF activities; and (3) the presence of hydroxyl group or bulky group on C3 significantly reduced AF activities. A hydrolysis experiment using genistein, a typical active compound in this study, indicated that it was decomposed in the marine environment by hydrolysis reaction and that the degradation speed was significantly affected by pH. In a field AF test, genistein inhibited the attachment of B. amphitrite on panels coated with genistein-paint mixtures.     

Disruption of Ssp411 causes impaired sperm head formation and male sterility in mice

Background

We previously cloned the Ssp411 gene. We found that the Ssp411 protein is predominantly expressed in elongated spermatids in the rat testis in a stage-dependent manner. Although our findings strongly suggested that Ssp411 might play an important role in mammalian spermatogenesis, this hypothesis has not been studied.

Synergistic interactions between Glomus mosseae and Bradyrhizobium japonicum in enhancing proton release from nodules and hyphae

Soybean (Glycine max L. Merr.) seedlings were inoculated with Glomus mosseae (GM) and Bradyrhizobium japonicum (BJ) together or separately to study the effect of interactions on net H⁺ effluxes of nodules or extraradical hyphae by in vivo vibrating electrode techniques. GM promoted three-fold the H⁺ effluxes of nodules on mycorrhizal lateral roots and BJ increased eight-fold the net H⁺ effluxes of hyphae developing in the vicinity of nodules on lateral roots. Increments in plant P content were positively and linearly correlated with the net H⁺ efflux of nodules and hyphae. It is concluded that increased H⁺ effluxes of nodules resulted from enhanced nitrogenase activities induced by the presence of the AM fungus in lateral roots. The results point to additive effects of interactions between mycorrhizal fungi and rhizobia in increasing the extent of acidification of the “nodulesphere” and the hyposphere.     

Temporal properties of dual-peak responses of mouse retinal ganglion cells and effects of inhibitory pathways

Dual-peak responses of retinal ganglion cells (RGCs) are observed in various species, previous researches suggested that both response peaks were involved in retinal information coding. In the present study, we investigated the temporal properties of the dual-peak responses recorded in mouse RGCs elicited by spatially homogeneous light flashes and the effect of the inhibitory inputs mediated by GABAergic and/or glycinergic pathways. We found that the two peaks in the dual-peak responses exhibited distinct temporal dynamics, similar to that of short-latency and long-latency single-peak responses respectively. Pharmacological studies demonstrated that the application of exogenous GABA or glycine greatly suppressed or even eliminated the second peak of the cells’ firing activities, while little change was induced in the first peak. Co-application of glycine and GABA led to complete elimination of the second peak. Moreover, application of picrotoxin or strychnine induced dual-peak responses in some cells with transient responses by unmasking a second response phase. These results suggest that both GABAergic and glycinergic pathways are involved in the dual-peak responses of the mouse RGCs, and the two response peaks may arise from distinct pathways that would converge on the ganglion cells.     

克雷伯氏菌甘油脱氢酶dhaD的克隆表达、纯化及酶学性质研究

以克雷伯氏菌基因组DNA为模板,扩增得到编码甘油脱氢酶（GDH）的基因dhaD,将其克隆到大肠杆菌表达载体pET-28a(+)上,在E.coliBL21（DE3）中诱导表达,利用表达载体pET-28a(+)上的6·His-Tag标记选用Ni柱亲和层析法纯化表达具有活性的甘油脱氢酶(GDH),纯化后比酶活达到156U/mg,纯化倍数达4.6倍,回收率为67.4%。并初步研究了该酶的酶学性质,酶反应的最适pH为11.0,在pH7.0～12.0范围内稳定;酶反应的最适温度为30℃,稳定范围为25～45℃; 酶动力学参数以甘油为底物的Km为0.54 mmol/L, Vmax为0.49 μmol/(mL·min)。     

Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression

Despite increasing evidence for the existence of antigen-specific regulatory T cells, the mechanisms underlying suppression remain unclear. In this study we have identified and cloned a novel subset of antigen-specific regulatory T cells and demonstrated that these T cells possess a unique combination of cell surface markers and array of cytokines. The regulatory T cells are able to inhibit the function of T cells carrying the same T-cell receptor specificity and prevent skin allograft rejection in an antigen-specific, dose-dependent manner. The regulatory T cells are able to acquire alloantigen from antigen-presenting cells, present the alloantigen to activated syngeneic CD8+ T cells and then send death signals to CD8+ T cells. These findings provide a novel mechanism of regulatory T-cell-mediated, antigen-specific suppression.     

Apigenin enhances the cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand in human rheumatoid arthritis fibroblast-like synoviocytes

Activated rheumatoid arthritis (RA) fibroblast-like synoviocytes (RAFLSs) play a central role in both initiating and driving RA. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been documented to induce apoptosis only in a small proportion of RAFLSs, which is followed by an induction of proliferation in surviving cells. Apigenin, a chemopreventive bioflavonoid, exhibits proapoptotic activity in many types of cells. In the present study, we sought to determine whether apigenin could enhance the cytotoxic effect of TRAIL on activated RAFLSs. Human RAFLSs isolated from patients with RA were treated with TRAIL (1 nM), apigenin (20 μM), or their combination, and subjected to apoptosis analysis after a 24-h incubation and proliferation analysis after a 72-h incubation. Apoptosis assay revealed that TRAIL or apigenin alone induced a marked apoptosis in RAFLS and their combination yielded a synergistic increase in RAFLS apoptosis. Immunoblotting analysis of apoptosis regulators demonstrated that combined treatment with apigenin increased caspase-3 expression and activity and decreased the Bcl-2/Bax ratio relative to treatment with TRAIL alone. The presence of apigenin significantly restrained TRAIL-induced RAFLS proliferation, coupled with restoration of the expression of two cell-cycle inhibitors p21 and p27. Moreover, the combination with apigenin blunted TRAIL-induced activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Our data collectively demonstrate that apigenin sensitizes RAFLS to TRAIL-induced apoptosis and counteracts TRAIL-dependent RAFLS proliferation, which is likely mediated through inactivation of PI3-K/Akt signaling pathway.