BioAssay Research Database (BARD): chemical biology and probe-development enabled by structured metadata and result types.

BARD, the BioAssay Research Database (https://bard.nih.gov/) is a public database and suite of tools developed to provide access to bioassay data produced by the NIH Molecular Libraries Program (MLP). Data from 631 MLP projects were migrated to a new structured vocabulary designed to capture bioassay data in a formalized manner, with particular emphasis placed on the description of assay protocols. New data can be submitted to BARD with a user-friendly set of tools that assist in the creation of appropriately formatted datasets and assay definitions. Data published through the BARD application program interface (API) can be accessed by researchers using web-based query tools or a desktop client. Third-party developers wishing to create new tools can use the API to produce stand-alone tools or new plug-ins that can be integrated into BARD. The entire BARD suite of tools therefore supports three classes of researcher: those who wish to publish data, those who wish to mine data for testable hypotheses, and those in the developer community who wish to build tools that leverage this carefully curated chemical biology resource.

The Deuterator: software for the determination of backbone amide deuterium levels from H/D exchange MS data.

BACKGROUND: The combination of mass spectrometry and solution phase amide hydrogen/deuterium exchange (H/D exchange) experiments is an effective method for characterizing protein dynamics, and protein-protein or protein-ligand interactions. Despite methodological advancements and improvements in instrumentation and automation, data analysis and display remains a tedious process. The factors that contribute to this bottleneck are the large number of data points produced in a typical experiment, each requiring manual curation and validation, and then calculation of the level of backbone amide exchange. Tools have become available that address some of these issues, but lack sufficient integration, functionality, and accessibility required to address the needs of the H/D exchange community. To date there is no software for the analysis of H/D exchange data that comprehensively addresses these issues. RESULTS: We have developed an integrated software system for the automated analysis and representation of H/D exchange data that has been titled "The Deuterator". Novel approaches have been implemented that enable high throughput analysis, automated determination of deuterium incorporation, and deconvolution of overlapping peptides. This has been achieved by using methods involving iterative theoretical envelope fitting, and consideration of peak data within expected m/z ranges. Existing common file formats have been leveraged to allow compatibility with the output from the myriad of MS instrument platforms and peptide sequence database search engines.A web-based interface is used to integrate the components of The Deuterator that are able to analyze and present mass spectral data from instruments with varying resolving powers. The results, if necessary, can then be confirmed, adjusted, re-calculated and saved. Additional tools synchronize the curated calculation parameters with replicate time points, increasing throughput. Saved results can then be used to plot deuterium buildup curves and 3D structural overlays. The system has been used successfully in a production environment for over one year and is freely available as a web tool at the project home page http://deuterator.florida.scripps.edu. CONCLUSION: The automated calculation and presentation of H/D exchange data in a user interface enables scientists to organize and analyze data efficiently. Integration of the different components of The Deuterator coupled with the flexibility of common data file formats allow this system to be accessible to the broadening H/D exchange community.

JavaShade: multiple sequence alignment box-and-shading on the World Wide Web.

RESULTS: JavaShade is a multiple sequence alignment box-and-shade tool for generating high quality printed output that uses a variety of methods for boxing and shading, allowing the most appropriate functions to be chosen for displaying the most meaningful positions in an alignment. AVAILABILITY: JavaShade is available from the WWW at http://industry.ebi.ac.uk/JavaShade

Orthopaedic complications of childhood neurofibromatosis.

Neurofibromatosis is a genetically transmitted, multisystemic disorder characterized by abnormalities of the skin, nervous tissue, and bone. Many of the serious problems associated with this disease are orthopaedic in nature. The treatment and plan of care for a child with neurofibromatosis must be comprehensive and consistent. Nursing care should address the developmental, physical, and emotional needs of the child, as well as the psychologic concerns and educational needs of the child and parents.

Orthopaedic complications of childhood neurofibromatosis.

Neurofibromatosis is a genetically transmitted, multisystemic disorder characterized by abnormalities of the skin, nervous tissue, and bone. Many of the serious problems associated with this disease are orthopaedic in nature. The treatment and plan of care for a child with neurofibromatosis must be comprehensive and consistent. Nursing care should address the developmental, physical, and emotional needs of the child, as well as the psychologic concerns and educational needs of the child and parents.

Studies on the etiology of trace metal-induced porphyria: effects of porphyrinogenic metals on coproporphyrinogen oxidase in rat liver and kidney.

Studies were conducted on the etiology of trace metal-induced porphyria in rats, with particular emphasis on the action of metals on hepatic and renal coproporphyrinogen oxidase. Prolonged exposure of rats to methyl mercury hydroxide or sodium arsenate at subtoxic dose levels in drinking water resulted in a progressive coproporphyrinuria, reaching highest rates of coproporphyrin excretion 5 weeks after initiation of exposure. The development of coproporphyrinuria was accompanied by substantial metal accumulation in the kidney and a significant decrease in renal, but not hepatic, coproporphyrinogen oxidase activity. During prolonged exposure to either metal, the rates of coproporphyrin excretion and metal accumulation by the kidney continued to increase for 2 to 3 weeks following maximal inhibition of renal coproporphyrinogen oxidase. Acute treatment studies and studies in vitro support the conclusion that the kidney is the principal source of excess urinary coproporphyrin during metal exposure. These observations demonstrate that metal-induced coproporphyrinuria is predominantly of renal etiology and that impairment of renal coproporphyrinogen oxidase is a principal cause of this effect.