Towards a Reference Terminology for Ontology Research and Development in the Biomedical Domain

Ontology is a burgeoning field, involving researchers from the computer science, philosophy, data and software engineering, logic, linguistics, and terminology domains. Many ontology-related terms with precise meanings in one of these domains have different meanings in others. Our purpose here is to initiate a path towards disambiguation of such terms. We draw primarily on the literature of biomedical informatics, not least because the problems caused by unclear or ambiguous use of terms have been there most thoroughly addressed. We advance a proposal resting on a distinction of three levels too often run together in biomedical ontology research: 1. the level of reality; 2. the level of cognitive representations of this reality; 3. the level of textual and graphical artifacts. We propose a reference terminology for ontology research and development that is designed to serve as common hub into which the several competing disciplinary terminologies can be mapped. We then justify our terminological choices through a critical treatment of the ‘concept orientation’ in biomedical terminology research

Capabilities of miR-24 in exosomes in breast cancer cells

Circulating tumor cells are cells that break away from a primary malignant site and circulate in the blood stream. From there, they can relocate to another part of the body, and cause metastasis. They can be used as biomarkers for cancer prognosis, and may also be used for cancer diagnosis in the presence of comorbid conditions. Micro RNAs (miRNA) are non-coding small RNAs found in humans that can degrade or upregulate protein transcription. miRNA is dependent on the Argonaute2 protein for incorporation into an RNA-induced silencing complex. miRNA utilizes exosomes to move outside the cytosol while being protected from extracellular enzymes such as RNases. miR-24 is implicated in many cancers, including breast cancer, and has the ability to upregulate the expression of its neighboring genes. As it has been shown that it can use the 3’untranslated regions on mRNA to influence expression of nearby targets, it also may influence its own transcription. The aim of this study was to evaluate the capability of transfected miR-24 to translocate into the nucleus of MCF-7 cells. It also evaluated the ability of transfected mirR-24 to integrate into exosomes, and whether this exosomal miRNA could similarly integrate into the nucleus in newly cultured cells. Results showed that transfected miR-24 does translocate into the nucleus of MCF-7 cells. It also showed that transfected miR-24 readily incorporates into exosomes. Because of procedural difficulties and time constraints, transfections with exosomal miR-24 have not yet been completed, but are a key next step in illustrating the ability of miR-24 to influence genetic expression on a broad spectrum. As miR-24 is upregulated in many disease states, including in many forms of breast cancer, the use of exosomes may outline a novel method for miRNA to integrate into malignant cells, and modulate protein transcription

Survey-based naming conventions for use in OBO Foundry ontology development

A wide variety of ontologies relevant to the biological and medical domains are available through the OBO Foundry portal, and their number is growing rapidly. Integration of these ontologies, while requiring considerable effort, is extremely desirable. However, heterogeneities in format and style pose serious obstacles to such integration. In particular, inconsistencies in naming conventions can impair the readability and navigability of ontology class hierarchies, and hinder their alignment and integration. While other sources of diversity are tremendously complex and challenging, agreeing a set of common naming conventions is an achievable goal, particularly if those conventions are based on lessons drawn from pooled practical experience and surveys of community opinion. We summarize a review of existing naming conventions and highlight certain disadvantages with respect to general applicability in the biological domain. We also present the results of a survey carried out to establish which naming conventions are currently employed by OBO Foundry ontologies and to determine what their special requirements regarding the naming of entities might be. Lastly, we propose an initial set of typographic, syntactic and semantic conventions for labelling classes in OBO Foundry ontologies. Adherence to common naming conventions is more than just a matter of aesthetics. Such conventions provide guidance to ontology creators, help developers avoid flaws and inaccuracies when editing, and especially when interlinking, ontologies. Common naming conventions will also assist consumers of ontologies to more readily understand what meanings were intended by the authors of ontologies used in annotating bodies of data

Weak association of anti-sperm antibodies and strong association of familial cryptorchidism/infertility with HLA-DRB1polymorphisms in prepubertal Ukrainian boys

<p>Abstract</p> <p>Background</p> <p>Cryptorchidism is a frequent syndrome occurring in 1-2% of males within the first year of age. Autoimmune reactions, particularly directed to testicular elements and/or spermatozoa have been found to be often associated with cryptorchidism. Therefore we investigated in this study the frequency of HLA class II alleles in order to recognize possible genetic predisposition for antisperm antibodies development in prepubertal boys with diagnosed cryptorchidism in Caucasoid population.</p> <p>Methods</p> <p>Sixty prepubertal boys with cryptorchidism and sixty healthy boys were examined for anti-sperm antibodies by indirect immunobead test as well as for their <it>HLA-DRB1 </it>and -<it>DQB1 </it>alleles using DNA obtained from peripheral blood leukocytes. The typing of <it>HLA-DRB1 </it>and -<it>DQB1 </it>was performed by using PCR-SSP low resolution method.</p> <p>Results</p> <p>Allele frequencies of <it>HLA-DRB1 </it>and <it>HLA-DQB1 </it>did not differ between boys with cryptorchidism and control boys. However, weakly significant differences in <it>DRB1*04 </it>(<it>p corrected </it>= 0.0475) and <it>DQB1*06 </it>(<it>p corrected </it>= 0.0385) were seen between cryptorchid patients with and without AsA, but none of these two patient groups differed significantly in <it>HLA </it>class II frequencies from controls except for AsA-negatives and <it>HLA-DQB1*06 </it>(<it>p corrected </it>= 0.0247). On the other hand, comparison of cryptorchid boys with familial cryptorchidism and/or infertility to control boys revealed highly significant (<it>p corrected </it>= 0.0006) difference in <it>HLA-DRB*11 </it>frequency, whereas boys with sporadic cryptorchidism did not differ from control. A much weaker, but still significant difference in <it>DRB*11 </it>frequency was also observed between boys with bilateral cryptorchidism and controls (<it>p corrected </it>= 0.037), whereas patients with unilateral cryptorchidism were not different from control in frequency of any <it>HLA-DRB1 </it>or -<it>DQB1 </it>allele tested.</p> <p>Conclusions</p> <p>Predisposition to produce anti-sperm antibodies seems to be only weakly associated with <it>HLA </it>class II genes, although this question requires further study on much larger population sample. It is plausible that familial and sporadic cryptorchidism may present distinct genetic background. The same may, to lower extent, apply to bilateral and unilateral cryptorchidism.</p

Survey-based naming conventions for use in OBO Foundry ontology development

<p>Abstract</p> <p>Background</p> <p>A wide variety of ontologies relevant to the biological and medical domains are available through the OBO Foundry portal, and their number is growing rapidly. Integration of these ontologies, while requiring considerable effort, is extremely desirable. However, heterogeneities in format and style pose serious obstacles to such integration. In particular, inconsistencies in naming conventions can impair the readability and navigability of ontology class hierarchies, and hinder their alignment and integration. While other sources of diversity are tremendously complex and challenging, agreeing a set of common naming conventions is an achievable goal, particularly if those conventions are based on lessons drawn from pooled practical experience and surveys of community opinion.</p> <p>Results</p> <p>We summarize a review of existing naming conventions and highlight certain disadvantages with respect to general applicability in the biological domain. We also present the results of a survey carried out to establish which naming conventions are currently employed by OBO Foundry ontologies and to determine what their special requirements regarding the naming of entities might be. Lastly, we propose an initial set of typographic, syntactic and semantic conventions for labelling classes in OBO Foundry ontologies.</p> <p>Conclusion</p> <p>Adherence to common naming conventions is more than just a matter of aesthetics. Such conventions provide guidance to ontology creators, help developers avoid flaws and inaccuracies when editing, and especially when interlinking, ontologies. Common naming conventions will also assist consumers of ontologies to more readily understand what meanings were intended by the authors of ontologies used in annotating bodies of data.</p

16(th) IHIW: population global distribution of killer immunoglobulin-like receptor (KIR) and ligands.

In the last fifteen years, published reports have described KIR gene-content frequency distributions in more than 120 populations worldwide. However, there have been limited studies examining these data in aggregate to detect overall patterns of variation at regional and global levels. Here, we present a summary of the collection of KIR gene-content data for 105 worldwide populations collected as part of the 15th and 16th International Histocompatibility and Immunogenetics Workshops, and preliminary results for data analysis

Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers

Multidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes, undergo a dramatic compartmentalization in lysosomes because of their hydrophobic weak base nature. We hence developed a novel photoactivation-based pharmacological Trojan horse approach to target and eradicate MDR cancer cells based on photo-rupture of IA-loaded lysosomes and tumor cell lysis via formation of reactive oxygen species. Illumination of IA-loaded cells resulted in lysosomal photodestruction and restoration of parental cell drug sensitivity. Lysosomal photodestruction of MDR cells overexpressing the key MDR efflux transporters ABCG2, ABCB1 or ABCC1 resulted in 10- to 52-fold lower IC(50) values of various IAs, thereby restoring parental cell sensitivity. Finally, in vivo application of this photodynamic therapy strategy after i.v. injection of IAs in human ovarian tumor xenografts in the chorioallantoic membrane model revealed selective destruction of tumors and their associated vasculature. These findings identify lysosomal sequestration of IAs as an Achilles heel of MDR cells that can be harnessed to eradicate MDR tumor cells via lysosomal photodestruction

Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice

Increasing evidence suggests that oxidative DNA damage accumulates in atherosclerosis. Recently, we showed that a genetic variant in the human DNA repair enzyme NEIL3 was associated with increased risk of myocardial infarction. Here, we explored the role of Neil3/NEIL3 in atherogenesis by both clinical and experimental approaches. Human carotid plaques revealed increased NEIL3 mRNA expression which significantly correlated with mRNA levels of the macrophage marker CD68. Apoe−/−Neil3−/− mice on high-fat diet showed accelerated plaque formation as compared to Apoe−/− mice, reflecting an atherogenic lipid profile, increased hepatic triglyceride levels and attenuated macrophage cholesterol efflux capacity. Apoe−/−Neil3−/− mice showed marked alterations in several pathways affecting hepatic lipid metabolism, but no genotypic alterations in genome integrity or genome-wide accumulation of oxidative DNA damage. These results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage

Removing the mustard oil bomb from seeds: transgenic ablation of myrosin cells in oilseed rape (Brassica napus) produces MINELESS seeds

Many plant phytochemicals constitute binary enzyme–glucoside systems and function in plant defence. In brassicas, the enzyme myrosinase is confined to specific myrosin cells that separate the enzyme from its substrate; the glucosinolates. The myrosinase-catalysed release of toxic and bioactive compounds such as isothiocyanates, upon activation or tissue damage, has been termed ‘the mustard oil bomb’ and characterized as a ‘toxic mine’ in plant defence. The removal of myrosin cells and the enzyme that triggers the release of phytochemicals have been investigated by genetically modifying Brassica napus plants to remove myrosinase-storing idioblasts. A construct with the seed myrosin cell-specific Myr1.Bn1 promoter was used to express a ribonuclease, barnase. Transgenic plants ectopically expressing barnase were embryo lethal. Co-expressing barnase under the control of the Myr1.Bn1 promoter with the barnase inhibitor, barstar, under the control of the cauliflower mosaic virus 35S promoter enabled a selective and controlled death of myrosin cells without affecting plant viability. Ablation of myrosin cells was confirmed with light and electron microscopy, with immunohistological analysis and immunogold-electron microscopy analysis showing empty holes where myrosin cells normally are localized. Further evidence for a successful myrosin cell ablation comes from immunoblots showing absence of myrosinase and negligible myrosinase activity, and autolysis experiments showing negligible production of glucosinolate hydrolysis products. The plants where the myrosin defence cells have been ablated and named ‘MINELESS plants’. The epithiospecifier protein profile and glucosinolate levels were changed in MINELESS plants, pointing to localization of myrosinases and a 35 kDa epithiospecifier protein in myrosin cells and a reduced turnover of glucosinolates in MINELESS plants