The MGED Ontology: a resource for semantics-based description of microarray experiments

MOTIVATION: The generation of large amounts of microarray data and the need to share these data bring challenges for both data management and annotation and highlights the need for standards. MIAME specifies the minimum information needed to describe a microarray experiment and the Microarray Gene Expression Object Model (MAGE-OM) and resulting MAGE-ML provide a mechanism to standardize data representation for data exchange, however a common terminology for data annotation is needed to support these standards. RESULTS: Here we describe the MGED Ontology (MO) developed by the Ontology Working Group of the Microarray Gene Expression Data (MGED) Society. The MO provides terms for annotating all aspects of a microarray experiment from the design of the experiment and array layout, through to the preparation of the biological sample and the protocols used to hybridize the RNA and analyze the data. The MO was developed to provide terms for annotating experiments in line with the MIAME guidelines, i.e. to provide the semantics to describe a microarray experiment according to the concepts specified in MIAME. The MO does not attempt to incorporate terms from existing ontologies, e.g. those that deal with anatomical parts or developmental stages terms, but provides a framework to reference terms in other ontologies and therefore facilitates the use of ontologies in microarray data annotation. AVAILABILITY: The MGED Ontology version.1.2.0 is available as a file in both DAML and OWL formats at http://mged.sourceforge.net/ontologies/index.php. Release notes and annotation examples are provided. The MO is also provided via the NCICB's Enterprise Vocabulary System (http://nciterms.nci.nih.gov/NCIBrowser/Dictionary.do). CONTACT: Stoeckrt@pcbi.upenn.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

Integrated Control of Acaricide-Resistant Boophilus Microplus Populations on Grazing Cattle in Mexico Using Vaccination with Gavac™ and Amidine Treatments

Throughout most of the twentieth century, tick infestations on cattle have been controlled with chemical acaricides, typically administered by dipping or spraying. This approach can cause environmental and residue problems and has created a high incidence of acaricide resistance within tick populations in the field. Recently we developed a vaccine against Boophilus microplus employing a recombinant Bm86 antigen preparation (Gavac), (Heber Biotec S.A., Havana, Cuba) which has been shown to induce a protective response in vaccinated animals. Here we show for the first time under field conditions a near 100% control of B. microplus populations resistant to pyrethroids and organophosphates, by an integrated system employing vaccination with Gavac and amidine treatments. This method effectively controls tick infestations while reducing the number of chemical acaricide treatments and consequently the rise of B. microplus populations resistant to chemical acaricides.     

Transglutaminase-catalyzed synthesis of trypsin-cyclodextrin conjugates: kinetics and stability properties

Bovine pancreatic trypsin was modified by the mono-6-amino-6-deoxy derivatives of alpha-, beta-, and gamma-cyclodextrin through a transglutaminase-catalyzed reaction. The trypsin-cyclodextrin conjugates, containing about 3 mol of oligosaccharide per mole of protein, were tested for their catalytic and stability properties. The specific esterolytic activity and the kinetics constants of trypsin were significantly improved following the transglutaminase-induced structural modifications. Trypsin-cyclodextrin conjugates were also found markedly (sixfold) more resistant to autolytic degradation at alkaline pH, and their thermal stability profile was improved by about 16 degrees C. Moreover, they were particularly resistant to heat inactivation when treated at different temperatures ranging from 45 degrees C to 70 degrees C for different periods of time.     

Effects of beta-cyclodextrin-dextran polymer on stability properties of trypsin

Dextran modified with the mono-6-pentylene-diamino-6-deoxy-beta-cyclodextrin derivative was evaluated as a thermoprotectant additive for trypsin. The optimum temperature for trypsin activity was increased by 7 degrees C in the presence of this polymer. The enzyme thermostability was increased from 48.5 to 64 degrees C over 10 min of incubation, and the activation free energy of thermoinactivation at 50 degrees C was increased by 4.1 kJ/mol in the presence of the additive. Trypsin was 6-fold more resistant to autolytic inactivation at alkaline pH in the presence of the polymer.     

Cytotoxicity of the E(2)-isoprostane 15-E(2t)-IsoP on oligodendrocyte progenitors

Oxidant stress plays a significant role in the pathogenesis of periventricular leukomalacia (PVL). Isoprostanes (IsoPs) are bioactive products of lipid peroxidation abundantly generated during hypoxic-ischemic injuries. Because loss of oligodendrocytes (OLs) occurs early in PVL, we hypothesized that IsoPs could induce progenitor OL death. 15-E(2t)-IsoP but not 15-F(2t)-IsoP elicited a concentration-dependent death of progenitor OLs by oncosis and not by apoptosis, but exerted minimal effects on mature OLs. 15-E(2t)-IsoP-induced cytotoxicity could not be explained by its conversion into cyclopentenones, because PGA(2) was hardly cytotoxic. On the other hand, thromboxane A(2) (TxA(2)) synthase inhibitor CGS12970 and cyclooxygenase inhibitor ibuprofen attenuated 15-E(2t)-IsoP-induced cytotoxicity. Susceptibility of progenitor OLs was independent of TxA(2) receptor (TP) expression, which was far less in progenitor than in mature OLs. However, TxA(2) synthase was detected in precursor but not in mature OLs, and TxA(2) mimetic U46619 induced hydroperoxides generation and progenitor OL death. The glutathione synthesis enhancer N-acetylcysteine prevented 15-E(2t)-IsoP-induced progenitor cell death. Depletion of glutathione in mature OLs with buthionine sulfoximine rendered them susceptible to cytotoxicity of 15-E(2t)-IsoP. These novel data implicate 15-E(2t)-IsoP as a product of oxidative stress that may contribute in the genesis of PVL.     

Stage-specific gene expression during Trypanosoma cruzi metacyclogenesis

The process of Trypanosoma cruzi metacyclogenesis involves the transformation of noninfective epimastigotes into metacyclic trypomastigotes, which are the pathogenic form. The analysis of stage-specific genes during T. cruzi metacyclogenesis may provide insight into the mechanisms involved in the regulation of gene expression in trypanosomatids. It may also improve the understanding of the mechanisms responsible for the pathology of Chagas disease, and could lead to the identification of new targets for chemotherapy of this disease. We have demonstrated that during metacyclogenesis the expression of several genes is controlled at the translational level by an alternative regulatory mechanism. This mechanism may involve the mobilization of mRNA to the translation machinery. We have been using self-made T. cruzi microarrays to investigate the role of polysomal mobilization in modulating gene expression during metacyclogenesis.     

caCORE: a common infrastructure for cancer informatics

MOTIVATION:Sites with substantive bioinformatics operations are challenged to build data processing and delivery infrastructure that provides reliable access and enables data integration. Locally generated data must be processed and stored such that relationships to external data sources can be presented. Consistency and comparability across data sets requires annotation with controlled vocabularies and, further, metadata standards for data representation. Programmatic access to the processed data should be supported to ensure the maximum possible value is extracted. Confronted with these challenges at the National Cancer Institute Center for Bioinformatics, we decided to develop a robust infrastructure for data management and integration that supports advanced biomedical applications. RESULTS: We have developed an interconnected set of software and services called caCORE. Enterprise Vocabulary Services (EVS) provide controlled vocabulary, dictionary and thesaurus services. The Cancer Data Standards Repository (caDSR) provides a metadata registry for common data elements. Cancer Bioinformatics Infrastructure Objects (caBIO) implements an object-oriented model of the biomedical domain and provides Java, Simple Object Access Protocol and HTTP-XML application programming interfaces. caCORE has been used to develop scientific applications that bring together data from distinct genomic and clinical science sources. AVAILABILITY: caCORE downloads and web interfaces can be accessed from links on the caCORE web site (http://ncicb.nci.nih.gov/core). caBIO software is distributed under an open source license that permits unrestricted academic and commercial use. Vocabulary and metadata content in the EVS and caDSR, respectively, is similarly unrestricted, and is available through web applications and FTP downloads. SUPPLEMENTARY INFORMATION: http://ncicb.nci.nih.gov/core/publications contains links to the caBIO 1.0 class diagram and the caCORE 1.0 Technical Guide, which provide detailed information on the present caCORE architecture, data sources and APIs. Updated information appears on a regular basis on the caCORE web site (http://ncicb.nci.nih.gov/core).