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At least 271 records · Page 15Linked to original sources

Noise or fugue: seeking the logic of child health indicators.

Despite improvements in many child health indicators, several important ones, including the racial disparity in infant mortality, have not improved in recent years. A focus on dramatic but rare risk factors has distracted attention away from the primary determinants of these indicators. An analytic model to assess these indicators identifies three interacting determinates: (a) social well-being, (b) our technical capacity to reduce the risk that low social status conveys, and (c) our performance in providing access to this technical capacity. These three determinants can move independently and can, therefore, mask important trends in social status and the impact of programs and policies.

Child Welfare↗

Comparative analysis of two slc11 (Nramp) loci in Takifugu rubripes.

To study the evolution of the solute carrier family 11 (slc11; formerly Nramp) protein, we isolated and characterized two paralogs from the pufferfish Takifugu rubripes (Fugu). These teleost genes, designated Fugu slc11a-a and Fugu slc11a-b, comprise open reading frames of 1743 nucleotides (581 amino acids) and 1662 nt (554 aa), respectively. The proteins are 81% similar, and both exhibit signature features of the slc11 family of proteins including 12 transmembrane domains, a conserved transport motif and a glycosylated loop. Both Fugu paralogs are more Slc11a2-like based on sequence homology and phylogenetic studies. Analysis of gene environment placed both in the proximity of multiple loci syntenic to human chromosome 12q13, that is, within a SLC11A2 gene environment. However, Fugu slc11a-a also gave one match with chromosome 2q35, where human SLC11A1 resides. Functional diversification was suggested by differences in tissue distribution and subcellular localization. Fugu slc11a-a exhibits a restricted expression profile and a complex subcellular localization, including LAMP1 positive late endosomes/lysosomes in transiently transfected mouse macrophages. Fugu slc11a-b is expressed ubiquitously and localizes solely to late endosomes/lysosomes. This comparative analysis extends our understanding of the evolution and function of this important family of divalent cation transporters. [Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AJ496547/8/9 and AJ496550.]

Amino Acid Sequence↗

Analysis of pufferfish homologues of the AT-rich human APP gene.

Mutations in the beta-amyloid precursor protein (APP) gene are associated with some forms of Familial Alzheimer's Disease. The human APP gene is large, the 19 exons span approximately 300 kb, and AT-rich, at 40% GC. We have examined the genomic structure and cDNA sequence of the APP gene in the pufferfish Fugu rubripes and Tetraodon fluviatilis, respectively. In contrast to human, the Fugu APP gene spans less than 10 kb of DNA, with the introns compacted 48-fold on average. Two axons, alternatively processed in humans, are absent in both pufferfish. APP is the largest, most AT-rich gene examined in Fugu and is also the most highly compressed. The genomic sequences spanning the human and the Fugu APP genes were analysed with a set of exon and gene prediction programs. Results show that these are highly reliable for the Fugu gene with lower false positive and false negative rates than are seen in the analysis of the human gene. Comparative analysis of Fugu sequences homologous to very AT-rich regions in the human genome may, therefore, be advantageous in gene-finding efforts, both for their highly reduced sizes and their reliable gene predictions.

Alzheimer Disease↗

Oct2 transcription factors in fish--a comparative genomic analysis.

The Oct2 transcription factor is important in driving expression of the IgH locus of the channel catfish, Ictalurus punctatus. Two isoforms, catfish Oct2alpha and Oct2beta, have been characterized at the level of expression and function, but little is known of the structure of the Oct2 gene in catfish. To gain insight into the diversity of Oct2 gene structure and expression in the teleost fish, a comparative genomic analysis of Oct2 was undertaken in the pufferfish (Fugu rubripes) and the zebrafish (Danio rerio). The orthologues of zebrafish and Fugu Oct2 were identified, and share with catfish Oct2 the expression of a limited number (two in zebrafish, three in Fugu) of isotypes produced by alternative pathways of RNA processing. The alternatively spliced variants of catfish Oct2 showed a different pattern of exon use from those of Fugu and zebrafish. The analysis also identified a novel homologue of Oct2 in both zebrafish and Fugu. This homologue, termed Oct2x, shares similarities to both Oct1 and Oct2. A phylogenetic analysis of the relationships of Oct2x gave an unexpected result, with Oct2x occupying a position basal to the Oct gene families of both vertebrates and Drosophila.

Alternative Splicing↗