Franklin H. Norris

Genome of the Bacterium Streptococcus pneumoniae Strain R6

Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans. Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S. pneumoniae R6. Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen. It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria. In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted. Among those proteins there may be new targets for vaccine and antibiotic development.

Conservation of the sequence of the Alzheimer's disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis

Neuritic plaque and cerebrovascular amyloid deposits have been detected in the aged monkey, dog, and polar bear and have rarely been found in aged rodents (Biochem. Biophy. Res. Commun., 12 (1984) 885-890; Proc. Natl. Acad. Sci. U.S.A., 82 (1985) 4245-4249). To determine if the primary structure of the 42-43 residue amyloid peptide is conserved in species that accumulate plaques, the region of the amyloid precursor protein (APP) cDNA that encodes the peptide region was amplified by the polymerase chain reaction and sequenced. The deduced amino acid sequence was compared to those species where amyloid accumulation has not been detected. The DNA sequences of dog, polar bear, rabbit, cow, sheep, pig and guinea pig were compared and a phylogenetic tree was generated. We conclude that the amino acid sequence of dog and polar bear and other mammals which may form amyloid plaques is conserved and the species where amyloid has not been detected (mouse, rat) may be evolutionarily a distinct group. In addition, the predicted secondary structure of mouse and rat amyloid that differs from that of amyloid bearing species is its lack of propensity to form a beta sheeted structure. Thus, a cross-species examination of the amyloid peptide may suggest what is essential for amyloid deposition.

Effects of naloxone and acetylcholine on medial thalamic and cortical units in naive and morphine dependent rats

Abstract An important role has been suggested for acetylcholine (ACh) in both the development and the expression of dependence upon morphine (1). However, the specific nature of this role has not been established. Much recent evidence implicates the medial thalamic (m. thalamic) region in the genesis of these phenomena. In particular, Wei et al. (2) report this area to be one of the most effective brain regions for the precipitation of withdrawal (WD) in opiate dependent rats by the direct implantation of naloxone. Furthermore, electrical stimulation of the m. thalamic region of naive rats can produce a series of responses reminiscent of the morphine WD syndrome (unpublished observations). Thus naloxone may precipitate WD in opiate dependent animals by exciting neurons in the m. thalamic region which are not similarly excited in naive animals. It might do this by releasing increased stores of ACh onto receptors made supersensitive secondary to inhibition of ACh release by morphine (2,3,4). However, recent work suggests that such a simplistic mechanism is probably inadequate to explain opiate WD (1). The present experiments were performed to test this theory more directly using the technique of microiontophoresis. The results indicate that the number of neurons excited by naloxone is increased in m. thalamus, but not cerebral cortex, of dependent animals. However, this cannot be attributed simply to a release of ACh by naloxone and receptors appear subsensitive rather than supersensitive to ACh in dependent animals.

Computerized graphic methods for determining dissociation constants of agonists, partial agonists, and competitive antagonists in isolated smooth muscle preparations

Computer programs have been written that calculate dissociation constants for agonists, partial agonists, and competitive antagonists from data generated in isolated smooth muscle preparations. The data are analyzed according to standard procedures and are presented in graphical form with the aid of an inexpensive digital plotter. The digital plotter coupled with a computer markedly decreases the time required to perform these fundamental analyses and also reduces the chance for error and experimenter bias.

Alzheimer's disease amyloid peptide is encoded by two exons and shows similarity to soybean trypsin inhibitor

To better understand the processing of the Alzheimer disease amyloid precursor protein, we have cloned and sequenced that region of the human genome coding for the amyloid peptide. Two exons separated by a 6.2kb intron define this region. Characterization of the A4 peptide amino acid sequence shows similarity to the structure of soybean trypsin inhibitor (Kunitz). Our observation describes a different region of PreA4 than the previously characterized domain of larger amyloid precursor molecules PreA4 751 and 770(2). Moreover, the exon organization, Kunitz domain duplication and transmembrane location of A4 suggest that PreA4 is similar to growth factor precursors and thus may be processed similarly.

GENEVIEW and the DNACE data bus: computational tools for analysis, display and exchange of genetic information

We describe an interactive computational tool, GENEVIEW, that allows the scientist to retrieve, analyze, display and exchange genetic information. The scientist may request a display of information from a GenBank locus, request that a restriction map be computed, stored and superimposed on GenBank information, and interactively view this information. GENEVIEW provides an interface between the GenBank data base and the programs of the Lilly DNA Computing Environment (DNACE). This interface stores genetic information in a simple, free format that has become the universal convention of DNACE; this format will serve as the convention for all future software development at Eli Lilly and Company, and could serve as a convention for genetic information exchange.

ANPLASMAP: a computational tool for the interactive display of restriction maps on alphanumeric terminal devices

Abstract We describe an interactive computational tool, ANPLASMAP, that allows the scientist to interactively retrieve and display DNA fragment or plasmid restriction maps. ANPLASMAP is fully compatible with the previously described color graphics plasmid storage, retrieval and display system, PLASMAP; however, ANPLASMAP will operate on commonly-available, inexpensive ANSI terminal devices and calls no other software packages.