An integrated text mining framework for metabolic interaction network reconstruction

Text mining (TM) in the field of biology is fast becoming a routine analysis for the extraction and curation of biological entities (e.g., genes, proteins, simple chemicals) as well as their relationships. Due to the wide applicability of TM in situations involving complex relationships, it is valuable to apply TM to the extraction of metabolic interactions (i.e., enzyme and metabolite interactions) through metabolic events. Here we present an integrated TM framework containing two modules for the extraction of metabolic events (Metabolic Event Extraction module—MEE) and for the construction of a metabolic interaction network (Metabolic Interaction Network Reconstruction module—MINR). The proposed integrated TM framework performed well based on standard measures of recall, precision and F-score. Evaluation of the MEE module using the constructed Metabolic Entities (ME) corpus yielded F-scores of 59.15% and 48.59% for the detection of metabolic events for production and consumption, respectively. As for the testing of the entity tagger for Gene and Protein (GP) and metabolite with the test corpus, the obtained F-score was greater than 80% for the Superpathway of leucine, valine, and isoleucine biosynthesis. Mapping of enzyme and metabolite interactions through network reconstruction showed a fair performance for the MINR module on the test corpus with F-score >70%. Finally, an application of our integrated TM framework on a big-scale data (i.e., EcoCyc extraction data) for reconstructing a metabolic interaction network showed reasonable precisions at 69.93%, 70.63% and 46.71% for enzyme, metabolite and enzyme–metabolite interaction, respectively. This study presents the first open-source integrated TM framework for reconstructing a metabolic interaction network. This framework can be a powerful tool that helps biologists to extract metabolic events for further reconstruction of a metabolic interaction network. The ME corpus, test corpus, source code, and virtual machine image with pre-configured software are available atwww.sbi.kmutt.ac.th/ preecha/metrecon.

Specimens For Observing Single Events Of Dna Metabolism By Fluorescence Microscopy

Single stained DNA molecules can be visualized by fluorescence microscopy (1). Therefore, perhaps single events of DNA metabolism can also be visualized by fluorescence microscopy. Problems to solve include (a) photobleaching of stained DNA, (b) photolytic damage to macromolecules necessary for metabolism, including DNA, (c) inhibition of metabolism by the process of preparation of the specimen, and (d) interference with image formation by macromolecules that either must be or by chance are present during metabolism. These problems have been solved, at least in part, during a study of the in vitro packaging of bacteriophage T7 (2). Packaging occurs in T7 capsids that had previously been assembled without assistance of DNA. The DNA substrate for packaging is a head-to-tail multimer (concatemer) of the terminally repetitious, nonpermuted T7 DNA. The metabolic event observed in ref. 2 was capsid-dependent specific cleavage of concatemers during packaging. The concatemers had formed a DNA network before cleavage.

Collagen-induced platelet activation mainly involves the protein kinase C pathway

This study analyses early biochemical events in collagen-induced platelet activation. An early metabolic event occurring during the lag phase was the activation of PtdIns(4,5)P2-specific phospholipase C. Phosphatidic acid (PtdOH) formation, phosphorylation of P43 and P20, thromboxane B2 (TXB2) synthesis and platelet secretion began after the lag phase, and were similarly time-dependent, except for TXB2 synthesis, which was delayed. Collagen induced extensive P43 phosphorylation, whereas P20 phosphorylation was weak and always lower than with thrombin. The dose-response curves of P43 phosphorylation and granule secretion were similar, and both reached a peak at 7.5 micrograms of collagen/ml, a dose which induced half-maximal PtdOH and TXB2 formation. Sphingosine, assumed to inhibit protein kinase C, inhibited P43 phosphorylation and secretion in parallel. However, sphingosine was not specific for protein kinase C, since a 15 microM concentration, which did not inhibit P43 phosphorylation, blocked TXB2 synthesis by 50%. Sphingosine did not affect PtdOH formation at all, even at 100 microM, suggesting that collagen itself induced this PtdOH formation, independently of TXB2 generation. The absence of external Ca2+ allowed the cleavage of polyphosphoinositides and the accumulation of InsP3 to occur, but impaired P43 phosphorylation, PtdOH and TXB2 formation, and secretion; these were only restored by adding 0.11 microM-Ca2+. In conclusion, stimulation of platelet membrane receptors for collagen initiates a PtdInsP2-specific phospholipase C activation, which is independent of external Ca2+, and might be the immediate receptor-linked response. A Ca2+ influx is indispensable to the triggering of subsequent platelet responses. This stimulation predominantly involves the protein kinase C pathway associated with secretion, and appears not to be mediated by TXB2, at least during its initial stage.

Effect of hepatic portal glucose concentration on food intake and metabolism

To examine the effect of different hepatic portal glucose concentrations on food intake and metabolism, rats were given hepatic portal or jugular infusions (83 microliters/min for 2 h) of 0.3, 0.6, and 1.2 M glucose, equiosmotic NaCl, or a mock control infusion. Food intake was decreased to the same extent by the three concentrations of glucose infused into the hepatic portal vein and unaffected by any concentration of glucose infused into the jugular vein. Parallel to the changes in food intake, hepatic glycogen content was increased by glucose infused into the hepatic portal vein but not jugular vein. Conversely, systemic plasma glucose levels were increased by glucose infused into the jugular vein but not hepatic portal vein. Plasma insulin levels increased to the same extent irrespective of the route of infusion. Food intake was unaffected by the osmolarity of glucose infused into the hepatic portal vein, but was decreased by hyperosmotic NaCl control infusions. Hyperosmotic NaCl infusions also elevated levels of circulating fat fuels, indicating a stress response. The results show that the critical metabolic event in the liver that influences food intake is only indirectly coupled to the concentration of glucose in the hepatic portal vein.