Novel natriuretic peptides from the venom of the inland taipan (Oxyuranus microlepidotus): isolation, chemical and biological characterisation

Three natriuretic-like peptides (TNP-a, TNP-b, and TNP-c) were isolated from the venom of Oxyuranus microlepidotus (inland taipan) and were also present in the venoms of Oxyuranus scutellatus canni (New Guinea taipan) and Oxyuranus scutellatus scutellatus (coastal taipan). They were isolated by HPLC, characterised by mass spectrometry and Edman analysis, and consist of 35-39 amino acid residues. These molecules differ from ANP/BNP through replacement of invariant residues within the 17-membered ring structure and by inclusion of proline residues in the C-terminal tail. TNP-c was equipotent to ANP in specific GC-A assays or aortic ring assays whereas TNP-a and TNP-b were either inactive (GC-A over-expressing cells and endothelium-denuded aortic rings) or weakly active (endothelium-in tact aortic rings). TNP-a and TNP-b were also unable to competitively inhibit the binding of TNP-c in endothelium-denuded aortae (GC-A) or endothelium-in tact aortae (NPR-C). Thus, these naturally occurring isoforms provide a new platform for further investigation of structure-function relationships of natriuretic peptides. (C) 2004 Elsevier Inc. All rights reserved.

Developing relational navigation to effectively understand software

Effective comprehension of complex software systems requires understanding of both the individual documents that represent software and the complex relationships that exist within and between documents. Relationships of all kinds play a vital role in a software engineer's comprehension of, and navigation within and between, software documents. User-determined relationships have the additional role of enabling the engineer to create and maintain relational documentation that cannot be generated by tools or derived from other relationships. We argue that for a software development environment to effectively support the understanding of complex software systems, relational navigation must be supported at both the document-focused (intra-document) and relation-focused (inter-document) levels. The need for a relation-focused approach is highlighted by an evaluation of an existing document-focused relational interface. We conclude with the requirements for a relation-focused approach to relational navigation. These requirements focus on the user's perspective when interacting with a collection of related documents. We define the requirements for a software development environment that effectively supports the understanding of the software documents and relationships that define a complex software system.