Formalizing planning and information search in naturalistic decision-making.

Decisions made by mammals and birds are often temporally extended. They require planning and sampling of decision-relevant information. Our understanding of such decision-making remains in its infancy compared with simpler, forced-choice paradigms. However, recent advances in algorithms supporting planning and information search provide a lens through which we can explain neural and behavioral data in these tasks. We review these advances to obtain a clearer understanding for why planning and curiosity originated in certain species but not others; how activity in the medial temporal lobe, prefrontal and cingulate cortices may support these behaviors; and how planning and information search may complement each other as means to improve future action selection.

The PIR-International Protein Sequence Database.

From its origin the Protein Information Resource (http://www-nbrf. georgetown.edu/pir/) has supported research on evolution and computational biology by designing and compiling a comprehensive, quality controlled, and well-organized protein sequence database. The database has been produced and updated on a regular schedule since 1984. Since 1988 it has been maintained collaboratively by the PIR-International, an association of data collection centers engaged in international cooperation for the development of this research resource during a period of explosive acquisition of new data. As of June 1997, essentially all sequence entries have been classified into families, allowing the efficient application of methods to propagate and standardize annotation among related sequences. The databases are available through the Internet by the World-Wide Web and FTP, or on CD-ROM and magnetic media.

The effect of interleukin-1 beta and interleukin-4 on the expression of prostaglandin receptors EP1 and EP3 in amnion WISH cells.

PROBLEM: Although prostaglandin E2 (PGE2) is believed to modulate biochemical and immunological events leading to parturition, the role of prostaglandin E receptors during labor has not been investigated. METHOD OF STUDY: Amnion WISH cells were incubated in media containing increasing concentrations of either interleukin-1 beta (IL-1 beta) or IL-4. Increased EP1 and EP3 protein expression was determined by Western blot analysis with peptide-specific antibodies. Concomitant measurements of culture media PGE2 were made by an enzyme immunoassay. RESULTS: Incubation of WISH cells with IL-1 beta or IL-4 caused a two- to three-fold increase in EP1 protein levels. IL-1 beta and IL-4 also caused six- and two-fold increases, respectively, in culture fluid PGE2 concentrations. IL-1 beta or IL-4 had no effect on EP3 protein levels. CONCLUSIONS: Based on these results, it is proposed that IL-1 beta and IL-4 may be involved in the initiation and promotion of labor by inducing EP1 levels and PGE2 production in amnion.

Analysis and organization of protein sequence data: a retrospective spanning four decades.

Protein sequence data are as useful and valuable today as was envisioned by pioneering sequencers and by the organizers of the first sequence database. Sequence analysis was first the province of specialists who developed search, comparison, and tree-building methods. Microcomputers, communication satellites, and the Internet have made these methods accessible to any scientist. The rapid increase in the data has driven a succession of changes in how databases are compiled, distributed, and accessed. Large public databases have become international collaborations. Although they need to develop still more efficient ways to accumulate, organize, annotate, and standardize huge amounts of data, inadequate support is available for such efforts. Thus there will be greater reliance on direct input from the scientific community. The World Wide Web is essential but not sufficient for integrated access to related databases.

The Protein Information Resource (PIR) and the PIR-International Protein Sequence Database.

From its origin, the PIR has aspired to support research in computational biology and genomics through the compilation of a comprehensive, quality controlled and well-organized protein sequence information resource. The resource originated with the pioneering work of the late Margaret O. Dayhoff in the early 1960s. Since 1988, the Protein Sequence Database has been maintained collaboratively by PIR-International, an association of macromolecular sequence data collection centers dedicated to fostering international cooperation as an essential element in the development of scientific databases. The work of the resource is widely distributed and is available on the World Wide Web, via FTP, E-mail server, CD-ROM and magnetic media. It is widely redistributed and incorporated into many other protein sequence data compilations including SWISS-PROT and theEntrezsystem of the NCBI.

Umbilical plasma erythropoietin correlations with blood gases and gestational age in appropriately grown infants.

Erythropoietin (EPO) levels were measured using an ELISA method in umbilical cord plasma from 68 appropriately grown neonates at 27 to 43 weeks of gestation (EGA). A consistent but small (5%) difference was found between the EPO levels in the umbilical artery (Ua), 21.0 +/- 2.5 mlU/mL (mean +/- SEM), and umbilical vein (Uv), 22.0 +/- 2.7 mlU/mL (p < 0.02, n = 30). Significant inverse correlations were found between Ua EPO levels and pO2 (r = -0.44, p < 0.002), pH (r = -0.68, p < 0.0001), as well as base deficit (r = -0.56, p < 0.0001). A significant correlation was found between EGA and Ua EPO from 27 to 43 weeks of gestation (r = 0.45, p < 0.001, n = 68). One and 5 minute Apgar scores did not correlate with EPO. These findings indicate that EPO correlates strongly with cord gas parameters and thus may serve as a clinically useful marker for both subacute fetal distress and chronic uteroplacental insufficiency.

Evolution of protein complexity: the blue copper-containing oxidases and related proteins.

The blue copper proteins and their relatives have been compared by sequence alignments, by comparison of three-dimensional structures, and by construction of phylogenetic trees. The group contains proteins varying in size from 100 residues to over 2,300 residues in a single chain, containing from zero to nine copper atoms, and with a broad variation in function ranging from electron carrier proteins and oxidases to the blood coagulation factors V and VIII. Difference matrices show the sequence difference to be over 90% for many pairs in the group, yet alignment scores and other evidence suggest that they all evolved from a common ancestor. We have attempted to delineate how this evolution took place and in particular to define the mechanisms by which these proteins acquired an ever-increasing complexity in structure and function. We find evidence for six such mechanisms in this group of proteins: domain enlargement, in which a single domain increases in size from about 100 residues up to 210; domain duplication, which allows for a size increase from about 170 to about 1,000 residues; segment elongation, in which a small segment undergoes multiple successive duplications that can increase the chain size 50-fold; domain recruitment, in which a domain coded elsewhere in the genome is added on to the peptide chain; subunit formation, to form multisubunit proteins; and glycosylation, which in some cases doubles the size of the protein molecule. Size increase allows for the evolution of new catalytic properties, in particular the oxidase function, and for the formation of coagulation factors with multiple interaction sites and regulatory properties. The blood coagulation system is examined as an example in which a system of interacting proteins evolved by successive duplications of larger parts of the genome. The evolution of size, functionality, and diversity is compared with the general question of increase in size and complexity in biology.

A region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC24, and the human breakpoint cluster gene, bcr.

Proto-dbl is a human proto-oncogene, whose oncogenic activation was initially detected by DNA transfection. We report significant sequence similarity between the predicted proto-dbl product and the products of CDC24, a Saccharomyces cerevisiae cell division cycle gene required for correct budding and establishment of cell polarity, and bcr, a gene implicated in the pathogenesis of chronic myelogenous leukemia (CML). Of 925 residues of the predicted proto-dbl protein, a stretch of 238 residues showed 29% and 22% identity over a region of similar length of the CDC24 and bcr proteins, respectively. When evolutionarily conservative substitutions were taken into account, the similarities were 68.8% and 71.6% for proto-dbl/CDC24 and proto-dbl/bcr gene products, respectively. Moreover, all three sequences were predicted to be markedly hydrophilic over this region. Very small deletions within the conserved region completely abolished transforming activity of dbl, while extensive deletion outside of this region had no effect. Even substitutions over a small stretch of close similarity with the other proteins substantially impaired transforming activity. Cells transformed by the dbl oncogene, like cdc24 mutants arrested at the nonpermissive temperature, form multinucleate cells. Thus, our findings indicate that the conserved region is an essential domain that may reflect important functional similarities among these otherwise highly divergent molecules.