Infectious Disease Ontology

Technological developments have resulted in tremendous increases in the volume and diversity of the data and information that must be processed in the course of biomedical and clinical research and practice. Researchers are at the same time under ever greater pressure to share data and to take steps to ensure that data resources are interoperable. The use of ontologies to annotate data has proven successful in supporting these goals and in providing new possibilities for the automated processing of data and information. In this chapter, we describe different types of vocabulary resources and emphasize those features of formal ontologies that make them most useful for computational applications. We describe current uses of ontologies and discuss future goals for ontology-based computing, focusing on its use in the field of infectious diseases. We review the largest and most widely used vocabulary resources relevant to the study of infectious diseases and conclude with a description of the Infectious Disease Ontology (IDO) suite of interoperable ontology modules that together cover the entire infectious disease domain

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

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Glutamate receptors mediate dynamic regulation of nitric oxide synthase expression in cerebellar granule cells

Nitric oxide (NO) is a multifaceted messenger molecule believed to be involved in neural plasticity and development. Within the cerebellum, the NO synthesizing enzyme, NO synthase (NOS), is expressed exclusively by granule cells and stellate/basket neurons. In the adult cerebellum, levels of NOS expression can be used to define discrete clusters of granule cell populations. Differential expression of NOS by granule cells temporally coincides with the establishment of afferent innervation of granule cells. In primary cerebellar cultures that comprise a functional network of glutamatergic and GABAergic cerebellar neurons, blockade of electrical activity by tetrodotoxin induced the expression of the neuronal isoform of NOS (nNOS) in granule cells. Conversely, direct depolarization of cultured neurons with K+ completely downregulated nNOS expression. Suppression of NMDA receptor- and AMPA receptor-mediated spontaneous synaptic signaling in cultured cells resulted in a drastic upregulation of nNOS expression in granule neurons. In contrast, blockade of GABAA receptor-mediated intercellular communication did not affect nNOS expression by granule cells. Blocking N-, P-, and Q-type voltage-dependent Ca2+ channels resulted in a graded upregulation of NOS expression, whereas manipulations of the cAMP- dependent signal transduction pathway induced no changes. We conclude that nNOS expression in developing cerebellar granule cells is regulated by excitatory neurotransmission and that calcium is an important signal transduction molecule involved in this regulatory process.</jats:p

Tenascins are associated with lipid rafts isolated from mouse brain

Lipid rafts are microdomains of the plasma membrane which are enriched in glycosphingolipids and specific proteins. The reported interactions of several raft-associated proteins (such as, e.g., F3) with tenascin C and tenascin R prompted us to consider that these oligomeric multidomain glycoproteins of the extracellular matrix (ECM) could associate with rafts. Here, we show punctate immunocytochemical distributions of tenascin C (TN-C) and tenascin R (TN-R) at the membrane surface of neural cells resembling the pattern reported for raft-associated proteins. Moreover, cholesterol depletion with methyl-beta-cyclodextrin reduced the punctate surface staining of TN-C. Consistently, TN-C was associated with lipid rafts of neonatal mouse brain according to sucrose density gradient centrifugation experiments. Furthermore, TN-R was also found in rafts prepared from myelin of adult mice. Thus, brain-derived tenascins are able to associate with lipid rafts. (C) 2002 Elsevier Science (USA). All rights reserved

Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells.

Engrailed transcription factors regulate survival, cell fate decisions and axon pathfinding in central neurons. En-2 can also attenuate Purkinje cell (PC) maturation. Here, we use array analysis to scrutinize gene expression in developing PCs overexpressing Engrailed-2 (L7En-2). The majority (70%) of regulated genes was found down-regulated in L7En-2 cerebella, consistent with the known repressive function of Engrailed-2. Differential gene expression, verified by in situ hybridization or Western blotting, was particularly evident during the first postnatal week, when L7En-2 PCs display conspicuous deficits in dendritogenesis. Functional classification revealed clusters of genes linked to vesicle formation and transport. Consistently, Golgi stacks located at the axonal pole of wild type PC somata were rarely detected in L7En-2 PCs. In addition, long continuous stretches of endoplasmic reticulum typically found around the axonal pole of wild type PCs were less frequently observed in transgenic cells. Engrailed-2 might therefore orchestrate PC survival and process formation as a regulator of subcellular organization