Researchers have documented microhabitat partitioning among the heteromyid rodents of the deserts of North America that may result from microhabitat specific predation rates; large/bipedal species predominate in the open/risky microhabitat and small/quadrupedal species predominate in the bush/safer microhabitat. Here, we provide direct experimental evidence on the role of predatory risk in affecting the foraging behavior of three species of heteromyid rodents: Arizona pocket mouse (Perognathus amplus; small/quadrupedal), Bailey's pocket mouse (P. baileyi; large/quadrupedal), and Merriam's kangaroo rat (Dipodomys merriami; large/bipedal). Both kangaroo rats and pocket mice are behaviorally flexible and able to adjust their foraging behavior to nightly changes in predatory risk. Under low levels of perceived predatory risk the kangaroo rat foraged relatively more in the open microhabitat than the two pocket mouse species. In response to the presence of barn owls, however, all three species shifted their habitat use towards the bush microhabitat. In response to direct measures of predatory risk, i.e. the actual presence of owls, all three species reduced foraging and left resource patches at higher giving up densities of seeds. In response to indirect indicators of predatory risk, i.e. illumination, there was a tendency for all three species to reduce foraging. The differences in morphology between pocket mice and kangaroo rats do appear to influence their behavioral responses to predatory risk.

The BCM Search Launcher is an integrated set of World Wide Web (WWW} pages that organize molecular biology-related search and analysis services available on the WWW by function, and provide a single point of entry for related searches. The Protein Sequence Search Page, for example, provides a single sequence entry form for submitting sequences to WWW servers that offer remote access to a variety of different protein sequence search tools, including BLAST, FASTA, Smith-Waterman, BEAUTY, PROSITE, and BLOCKS searches. Other Launch pages provide access to {I) nucleic acid sequence searches, (2} multiple and pair-wise sequence alignments, (3} gene feature searches, (4} protein secondary structure prediction, and (5) miscellaneous sequence utilities (e.g., six-frame translation). The BCM Search Launcher also provides a mechanism to extend the utility of other WWW services by adding supplementary hypertext links to results returned by remote servers. For example, links to the NCBI's Entrez data base and to the Sequence Retrieval System (SRS) are added to search results returned by the NCBI's WWW BLAST server. These links provide easy access to auxiliary information, such as Medline abstracts, that can be extremely helpful when analyzing BLAST data base hits. For new or infrequent users of sequence data base search tools, we have preset the default search parameters to provide the most informative first-pass sequence analysis possible. We have also developed a batch client interface for Unix and Macintosh computers that allows multiple input sequences to be searched automatically as a background task, with the results returned as individual HTML documents directly to the user's system. The BCM Search Launcher and batch client are available on the WWW at URL http://gc.bcm.tmc.edu:8088/search-launcher.html.DNA and protein sequence analysis services are now available from a large number of sources on the Internet, including Email, Gopher, and World Wide Web (WWW) servers (for review, see Boguski 1994;Harper 1994). These services are extremely useful for molecular biologists, as they allow access to the ever-expanding sequence data bases without requiring copious local data base storage, frequent data base updates, the cost of expensive and sophisticated hardware and software, and the cost and effort of continuous system maintenance.The development of the WWW, a hypertext- multimedia communications system on the Internet, has been particularly useful in making international biological resources readily available and more easy to use (Jacobson 1994;Harper 1995;Schatz and Hardin 1994). Analysis results returned by WWW servers are easy to view (one can move forward and backward through a document using slider bars), and a hypertext document can include any number of hypertext links, allowing direct access to a variety of additional information sources on the Internet (e.g., related documents and other services). Although comprehensive lists of molecular biology-related search and analysis resources currently available on the W...

BEAUTY [BLAST enhanced alignment utility] is an enhanced version of the NCBI's BLAST data base search tool that facilitates identification of thefunc--tions of matched sequences. We have created new data bases of conserved regions and functional domains for protein sequences in NCBI's Entrez data base, and BEAUTY allows this information to be incorporated directly into BLAST search results. A Conserved Regions Data Base, containing the locations of conserved regions within Entrez protein sequences, was constructed by [I] clustering the entire data base into families, [2} aligning each family using our PIMA multiple sequence alignment program, and [3] scanning the multiple alignments to locate the conserved regions within each aligned sequence. A separate Annotated Domains Data Base was constructed by extracting the locations of all annotated domains and sites from sequences represented in the Entrez, PROSITE, BLOCKS, and PRINTS data bases. BEAUTY performs a BLAST search of those Entrez sequences with conserved regions and/or annotated domains. BEAUTY then uses the information from the Conserved Regions and Annotated Domains data bases to generate, for each matched sequence, a schematic display that allows one to directly compare the relative locations of [1} the conserved regions, [2] annotated domains and sites, and [3} the locally aligned regions matched in the BLAST search. In addition, BEAUTY search results include World-Wide Web hypertext links to a number of external data bases that provide a variety of additional types of information on the function of matched sequences. This convenient integration of protein families, conserved regions, annotated domains, alignment displays, and World-Wide Web resources greatly enhances the biological informativeness of sequence similarity searches. BEAUTY searches can be performed remotely on our system using the "'BCM Search Launcher" World-Wide Web pages [URL is (http:/! gc.bcm.tmc.edu:80881 search-launcher / launcher.html)).The central goals of the human and model organism genome projects are to completely map and sequence the genes of these organisms. As work progresses, identification of the biochemical function of newly sequenced genes becomes a major challenge. Identification of gene function using traditional biochemical methods can be an extremely slow and laborious task that can take years of effort even for a single gene. Fortunately, computational methods are available that can greatly facilitate the identification of gene function. When a gene is isolated and sequenced, it can be matched against one or more of the publicly available sequence data bases, such as GenBank (Benson et al. 1993). If a similar gene of 1Corresponding author. EMAIL kworley@bcm.tmc.edu; known function can be identified in such a data base search, then the function of the newly sequenced gene can be surmised by analogy. The biochemical functions of a growing number of genes, including a number of inherited human disease genes (for review, see Collins 1995), are being determined in...

Type 2 diabetes (T2D), one of the most common diseases in the western world, is characterized by insulin resistance and impaired beta-cell function but currently it is difficult to determine the precise pathophysiology in individual T2D patients. Non-targeted metabolomics technologies have the potential for providing novel biomarkers of disease and drug efficacy, and are increasingly being incorporated into biomarker exploration studies. Contextualization of metabolomics results is enhanced by integration of study data from other platforms, such as transcriptomics, thus linking known metabolites and genes to relevant biochemical pathways. In the current study, urinary NMR-based metabolomic and liver, adipose, and muscle transcriptomic results from the db/db diabetic mouse model are described. To assist with cross-platform integration, integrative pathway analysis was used. Sixty-six metabolites were identified in urine that discriminate between the diabetic db/db and control db/+ mice. The combined analysis of metabolite and gene expression changes revealed 24 distinct pathways that were altered in the diabetic model. Several of these pathways are related to expected diabetes-related changes including changes in lipid metabolism, gluconeogenesis, mitochondrial dysfunction and oxidative stress, as well as protein and amino acid metabolism. Novel findings were also observed, particularly related to the metabolism of branched chain amino acids (BCAAs), nicotinamide metabolites, and pantothenic acid. In particular, the observed decrease in urinary BCAA catabolites provides direct corroboration of previous reports that have inferred that elevated BCAAs in diabetic patients are caused, in part, by reduced catabolism. In summary, the integration of metabolomics and transcriptomics data via integrative pathway mapping has facilitated the identification and contextualization of biomarkers that, presuming further analytical and biological validation, may be useful in future T2D clinical studies by identifying patient populations that share common disease pathophysiology and therefore may identify those patients that may respond better to a particular class of anti-diabetic drugs.

A multiple sequence alignment algorithm is described that uses a dynamic programming-based pattern construction method to align a set of homologous sequences based on their common pattern of conserved sequence elements. This pattern-induced multi-sequence alignment (PIMA) algorithm can employ secondary-structure dependent gap penalties for use in comparative modelling of new sequences when the three-dimensional structure of one or more members of the same family is known. We show that the use of secondary structure information can significantly improve the accuracy of aligning structure boundaries in a set of homologous sequences even when the structure of only one member of the family is known.