89 research outputs found

    Evolution of vertebrate genes related to prion and shadoo proteins – Clues for comparative genomic analysis

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    Recent findings of new genes in fish related to the prion protein (PrP) gene PRNP, including our recent report of SPRN coding for Shadoo (Sho) protein found also in mammals, raise issues of their function and evolution. Here we report additional novel fish genes found in public databases, including a duplicated SPRN gene, SPRNB, in Fugu, Tetraodon, carp, and zebrafish encoding the Sho2 protein, and we use comparative genomic analysis to analyze the evolutionary relationships and to infer evolutionary trajectories of the complete data set. Phylogenetic footprinting performed on aligned human, mouse, and Fugu SPRN genes to define candidate regulatory promoter regions, detected 16 conserved motifs, three of which are known transcription factor-binding sites for a receptor and transcription factors specific to or associated with expression in brain. This result and other homology-based (VISTA global genomic alignment; protein sequence alignment and phylogenetics) and context-dependent (genomic context; relative gene order and orientation) criteria indicate fish and mammalian SPRN genes are orthologous and suggest a strongly conserved basic function in brain. Whereas tetrapod PRNPs share context with the analogous stPrP-2 - coding gene in fish, their sequences are diverged, suggesting that the tetrapod and fish genes are likely to have significantly different functions. Phylogenetic analysis predicts the SPRN/SPRNB duplication occurred before divergence of fish from tetrapods, whereas that of stPrP-1 and stPrP-2 occurred in fish. Whereas Sho appears to have a conserved function in vertebrate brain, PrP seems to have an adaptive role fine-tuned in a lineage-specific fashion. An evolutionary model consistent with our findings and literature knowledge is proposed that has an ancestral prevertebrate SPRN-like gene leading to all vertebrate PrP-related and Sho-related genes. This provides a new framework for exploring the evolution of this unusual family of proteins and for searching for members in other fish branches and intermediate vertebrate groups

    Cloning and analysis of transcripts and genes encoding fish-specific proteins related to PrP

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    We report cloning and tissue expression of transcripts of a fourth fish-specific gene (SPRNB) encoding a prion protein (PrP)-related protein (Shadoo2) from two species, Cyprinus carpio (carp) and Danio rerio (zebrafish), as well as gene or partial transcript sequences identified by in silico searches of public databases from Gasterosteus aculeatus (stickleback), Oryzias latipes (medaka fish) and Salmo salar (salmon). We also present an up-to-date summary of current knowledge of the other three PrP-related genes and transcripts (PrP-like protein, PrP1 and PrP2) encoded exclusively in fish genomes, including some additional transcripts we identified by in silico searches. We compare levels of protein-sequence conservation among the different genes within given fish species, and among given genes in different fish species, and analyse the gene structures and contexts (flanking genes) where genomic sequence is available. These analyses show remarkably high divergences of sequences and expression patterns for proteins in distant fish, such as Fugu and zebrafish, leaving open the question of how varied their functions may be

    Empty spaces and the value of symbols: Estonia's 'war of monuments' from another angle

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    Taking as its point of departure the recent heightened discussion surrounding publicly sited monuments in Estonia, this article investigates the issue from the perspective of the country's eastern border city of Narva, focusing especially upon the restoration in 2000 of a 'Swedish Lion' monument to mark the 300th anniversary of Sweden's victory over Russia at the first Battle of Narva. This commemoration is characterised here as a successful local negotiation of a potentially divisive past, as are subsequent commemorations of the Russian conquest of Narva in 1704. A recent proposal to erect a statue of Peter the Great in the city, however, briefly threatened to open a new front in Estonia's ongoing 'war of monuments'. Through a discussion of these episodes, the article seeks to link the Narva case to broader conceptual issues of identity politics, nationalism and post-communist transition

    Shadoo, a new protein highly conserved from fish to mammals and with similarity to prion protein

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    We report evidence from cDNA isolation and expression analysis as well as analyses of genome, expressed sequence tag (EST), cDNA and expression databases for a new gene named SPRN (shadow of prion protein). SPRN comprises two exons, with the open reading frame (ORF) contained within exon 2, and codes for a protein of 130-150 amino acids named Shadoo (Japanese shadow), predicted to be extracellular and GPI-anchored. The SPRN gene was found in fish (zebrafish, Fugu) and mammals (mouse, rat, human). Conservation of order and transcription orientation of two proximal genes between fishes and mammals strongly indicates gene orthology. Sequence comparison shows: a highly conserved N-terminal signal sequence; Arg-rich basic region containing up to six tetrarepeats of consensus XXRG (where X is G, A or S); a hydrophobic region of 20 residues with strong homology to prion protein (PrP); a less conserved C-terminal domain containing a conserved glycosylation motif; and a C-terminal peptide predicted to be a signal sequence for glycophosphotidylinositol (GPI)-anchor attachment. Fish Shadoos (Sho) show well conserved sequences (identity 54%) over 106 amino acids (zebrafish length), and conservation among the mammalian sequences is very high (identity 81-96%). The fish and mammalian sequences are also well conserved, particularly for zebrafish, to beyond the end of the hydrophobic sequence (identity 41-53%, 78 amino acids, zebrafish length). The overall structure appears closely related to PrPs, although the C-terminal domains of Shos are quite different from those of PrPs, for which conformational changes in mammals are implicated in disease. The structural similarity is particularly interesting given recent reports of three new genes with similarities to PrPs found in Fugu (PrP-like, PrP-461/stPrP-1 and stPrP-2) and other fish, but for which direct evolution to higher vertebrate PrPs is unlikely and for which no other mammalian homologues have been found. Database information indicates expression of SPRN in embryo, brain and retina of mouse and rat, hippocampus of human, and in embryo and retina of zebrafish, and we directly confirmed a strikingly specific expression of the mammalian (human, mouse, rat) transcripts in whole brain. This result together with some common structural features led to the suggestive hypothesis of a possible functional link between mammalian PrP and Sho proteins

    Dihydrofolate reductase: the current story

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    Development of high-speed directly-modulated DFB and DBR lasers with surface gratings

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    The conventional distributed feedback and distributed Bragg reflector edge-emitting lasers employ buried gratings, which require two or more epitaxial growth steps. By using lateral corrugations of the ridge-waveguide as surface gratings the epitaxial overgrowth is avoided, reducing the fabrication complexity, increasing the yield and reducing the fabrication cost. The surface gratings are applicable to different materials, including Al-containing ones and can be easily integrated in complex device structures and photonic circuits. Single-contact and multiple contact edge-emitting lasers with laterally-corrugated ridge waveguide gratings have been developed both on GaAs and InP substrates with the aim to exploit the photon-photon resonance in order to extend their direct modulation bandwidth. The paper reports on the characteristics of such surface-grating-based lasers emitting both at 1.3 and 1.55 μm and presents the photon-photon resonance extended small-signal modulation bandwidth (> 20 GHz) achieved with a 1.6 mm long single-contact device under direct modulation. Similarly structured devices, with shorter cavity lengths are expected to exceed 40 GHz smallsignal modulation bandwidth under direct modulatio
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