Lightweight Expression of Granular Objects (LEGO) Content Modeling Using the SNOMED CT Observables Model to Represent Nursing Assessment Data.

This poster presentation presents a content modeling strategy using the SNOMED CT Observable Model to represent large amounts of detailed clinical data in a consistent and computable manner that can support multiple use cases. Lightweight Expression of Granular Objects (LEGOs) represent question/answer pairs on clinical data collection forms, where a question is modeled by a (usually) post-coordinated SNOMED CT expression. LEGOs transform electronic patient data into a normalized consumable, which means that the expressions can be treated as extensions of the SNOMED CT hierarchies for the purpose of performing subsumption queries and other analytics. Utilizing the LEGO approach for modeling clinical data obtained from a nursing admission assessment provides a foundation for data exchange across disparate information systems and software applications. Clinical data exchange of computable LEGO patient information enables the development of more refined data analytics, data storage and clinical decision support.

The C-terminal domain of myosin-like protein 1 (Mlp1p) is a docking site for heterogeneous nuclear ribonucleoproteins that are required for mRNA export.

For mRNA to be transported from the nucleus to the cytoplasm, it must travel from the site of transcription through the nuclear interior to the nuclear pore. Studies in Saccharomyces cerevisiae have suggested a relationship between poly(A) RNA trafficking and myosin-like protein 1 (Mlp1p), a nuclear-pore associated protein that is homologous to the mammalian Tpr (translocated promoter region) protein [Kosova, B., Panté, N., Rollenhagen, C., Podtelejnikov, A., Mann, M., Aebi, U., and Hurt, E. (2000) J. Biol. Chem. 275, 343-350]. We identified a yeast two-hybrid interaction between the C-terminal globular domain of Mlp1p and Nab2p, a shuttling heterogeneous nuclear ribonucleoprotein that is required for mRNA export. Coimmunoprecipitation confirms that Nab2p also interacts with full-length Mlp1p and in vitro binding experiments show that Nab2p binds directly to the C-terminal domain of Mlp1p. In addition, our experiments reveal that the C-terminal domain of Mlp1p is both necessary and sufficient to cause accumulation of poly(A) RNA and Nab2p in the nucleus. We propose a model where Mlp1p acts as a checkpoint at the nuclear pore by interacting with export-competent ribonucleoprotein complexes through its C-terminal globular domain. This study identifies Nab2p as a heterogeneous nuclear ribonucleoprotein found in complex with Mlp1p and begins to delineate the path that mRNA travels from the chromatin to the nuclear pore.

Influenza A viruses in feral Canadian ducks: extensive reassortment in nature.

The current dogma of influenza accepts that feral aquatic birds are the reservoir for influenza A viruses. Although the genomic information of human influenza A viruses is increasing, little of this type of data is available for viruses circulating in feral waterfowl. This study presents the genetic characterization of 35 viruses isolated from wild Canadian ducks from 1983 to 2000, as the first attempt at a comprehensive genotypic analysis of influenza viruses isolated from feral ducks. This study demonstrates that influenza virus genes circulating in Canadian ducks have achieved evolutionary stasis. The majority of these duck virus genes are clustered in distinct North American clades; however, some H6 and H9 genes are clustered with those from Eurasian viruses. Genes appeared to reassort in a random fashion. None of the genotypes identified remained present throughout all of the years examined and most PA and PB2 genes that crossed over into swine were clustered in one phylogenetic grouping. Additionally, matrix genes were identified that branch very early in the evolutionary tree. These findings demonstrate the diversity of the influenza virus gene pool in Canadian ducks, and suggest that genes which cluster in specific phylogenetic groupings in the PB2 and PA genes can be used for markers of viruses with the potential for crossing the species barrier. A more comprehensive study of this important reservoir is needed to provide further insight into the genomic composition of viruses that crossover the species barrier, which would be a useful component to pandemic planning.

Preparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics.

Options for the control of emerging and reemerging H5N1 influenza viruses include improvements in biosecurity and the use of inactivated vaccines. Commercially available H5N2 influenza vaccine prevents disease signs and reduces virus load but does not completely prevent virus shedding after challenge with H5N1 virus. By using reverse genetics, we prepared an H5N3 vaccine whose hemagglutinin is 99.6% homologous to that of A/CK/HK/86.3/02 (H5N1). We used the internal genes of A/PR/8/34 and the H5 of A/Goose/HK/437.4/99 (H5N1) after deletion of basic amino acids from its connecting peptide region. The resulting virus was not lethal to chicken embryos and grew to high HA titers in eggs, allowing preparation of HA protein-standardized vaccine in unconcentrated allantoic fluid. The N3 neuraminidase, derived from A/Duck/Germany/1215/73 (H2N3), permitted discrimination between vaccinated and naturally infected birds. The virus construct failed to replicate in quail and chickens. Similar to parental A/PR/8/34 (H1N1), it replicated in mice and ferrets and spread to the brains of mice; therefore, it should not be used as a live-attenuated vaccine. The H5N3 vaccine, at doses of 1.2 microg HA, induced HI antibodies in chickens and prevented death, signs of disease, and markedly reduced virus shedding after challenge with A/CK/HK/86.3/02 (H5N1) but did not provide sterilizing immunity. Thus, reverse genetics allows the inexpensive preparation of standardized, efficacious H5N3 poultry vaccines that may also reduce the reemergence of H5N1 genotypes.