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PubMed2006

Expression of fugu TIMP-3 and -4 genes in adult tissues and embryos.

The tissue inhibitors of metalloproteinases (TIMPs) are involved in various processes of extra-cellular matrix (ECM) metabolism by inhibiting matrix metalloproteinases (MMPs). However, the fundamental information for these genes is little known in fish. Previously, we report cDNA cloning and gene expressions of two fugu (Takifugu rubripes) TIMP-2s. Here, we cloned cDNA of fugu TIMP-3 and performed an expression analysis of TIMP-3 and -4 mRNA in fugu adult tissues using a quantitative real-time PCR. The expression level of TIMP-3 mRNA was constitutive in all tissues, while TIMP-4 was significantly higher in the brain (P=0.05). Further, we performed a whole mount in situ hybridization in fugu embryos at different stages. In early stages, TIMP-3 mRNA was abundant in the somites and the caudal end of the notochord. At hatching larvae, the TIMP-3 mRNA was abundant in the pectoral fin, dorsal and ventral fin fold along the entire antero-posterior axis. TIMP-3 may be involved in axis elongation and somitogenesis. TIMP-4 mRNA was expressed in the tail bud, at the midbrain-hindbrain boundary and in the diencephalon from 72 to 104 hpf. This indicates TIMP-4 is highly expressed in the brain matrix in vivo.

Amino Acid Sequence↗
PubMed2005

Convergent loss of an anciently duplicated, functionally divergent RH2 opsin gene in the fugu and Tetraodon pufferfish lineages.

We describe the complete opsin gene families from the sequenced fugu and Tetraodon pufferfish genomes. We report the convergent loss of function of an anciently duplicated, functionally divergent RH2 or "green-sensitive" opsin gene in both pufferfish lineages, designated RH2-2. In fugu, RH2-2 apparently ceased to function very recently following a transposon-induced deletion that truncated the N-terminal 115 amino acids from the translated protein. Although a lack of frameshift or nonsense mutations in the fugu RH2-2 pseudogene suggests that the gene was lost very recently in this lineage, we were unable to detect any evidence of a selective sweep associated with the fixation of the truncated allele from population data. Interspecific comparison of the remaining fugu RH2-2 coding sequence paradoxically indicates that the gene was under strong purifying selection until the truncation occurred.

Amino Acid Sequence↗
PubMed2004

A case of psychogenic fugue: I understand, aber ich verstehe nichts.

Psychogenic fugue is a disorder of memory that occurs following emotional or psychological trauma and results in a loss of one's personal past including personal identity. This paper reports a case of psychogenic fugue in which the individual lost access not only to his autobiographical memories but also to his native German language. A series of experiments compared his performance on a variety of memory and language tests to several groups of control participants including German-English bilinguals who performed the tasks normally or simulated amnesia for the German language. Neuropsychological, behavioral, electrophysiological and functional neuroimaging tests converged on the conclusion that this individual suffered an episode of psychogenic fugue, during which he lost explicit knowledge of his personal past and his native language. At the same time, he appeared to retain implicit knowledge of autobiographical facts and of the semantic or associative structure of the German language. The patient's poor performance on tests of executive control and reduced activation of frontal compared to parietal brain regions during lexical decision were suggestive of reduced frontal function, consistent with models of psychogenic fugue proposed by Kopelman and Markovitsch.

Adult↗
PubMed2004

Comparative analysis of a 229-kb medaka genomic region, containing the zic1 and zic4 genes, with Fugu, human, and mouse.

Medaka is one of the prominent model animals, which also include other fishes such as Fugu and zebrafish. Its genome is relatively compact but has not been well characterized. Here we have sequenced a 229-kb region of medaka, containing the Double anal fin (Da) locus, and compared its structure to those in Fugu, human, and mouse. This region, representing a gene-poor region, contains no major rearrangements and can be readily compared among different species. Comparison of G+C contents and repeats suggested that medaka and Fugu are highly related as expected and that medaka is more similar to mammals than Fugu is. Sequence comparisons of developmental genes zic1 and zic4, identified within this region, revealed that zic1, but not zic4, is highly conserved among vertebrates. The 5' coding region of zic4 is, however, extremely homologous among fishes with little synonymous substitutions, implying its distinct function in fish.

Amino Acid Sequence↗
PubMed2003

Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution.

The fugu (pufferfish) genome has been sequenced, and a second genome assembly was released 17 May 2002. Exhaustive searches were made to identify all P450 genes and pseudogenes from the earlier release of 26 October 2001. P450 genes assembled as completely as possible from these data were used to do additional searches of the newer assembly and all P450 genes and pseudogenes in the available fugu sequence data have been identified, compared to human P450s, and assigned names. There are 54 P450 genes in fugu and 1 nearly intact pseudogene (CYP3A50P). CYP1A is missing much of its N-terminal half; however, 45 P450 genes are completely assembled. Eight others are lacking only one or two exons or less. CYP2X4 is known only from an EST. This may be a 55th P450 gene if it represents an accurate sequence. In addition to 2X4, there are 16 other pseudogene fragments or small pieces of P450 genes. At the P450 family level, 17 of 18 mammalian families are found in fugu. CYP39 is the only CYP family missing and it is not seen in any other fish sequence data either. The CYP2 family shows the largest degree of divergence. In the CYP2 family, only CYP2R1 and CYP2U1 are conserved as recognizable subfamilies across species. Intron-exon boundaries are largely preserved across 420 million years of evolution.

Algorithms↗
PubMed1998

Hemispheric dominance in the processing of J.S. Bach fugues: a transcranial Doppler sonography (TCD) study with musicians.

Although the majority of studies on musical processing in musicians observed a left hemisphere dominance which has usually been explained by a proficient analytical strategy used by these subjects, the findings are still inconsistent. Changes in hemispheric activity induced by listening to music (J. S. Bach fugues) and by recognizing the repetitions of the fugue theme were examined, using the technique of bilateral transcranial Doppler sonography (TCD) of the left and right middle cerebral artery (MCA). Subjects were 32 right-handed musicians, half of whom were members of an orchestra or members of a choir. The fugues were presented in two versions: a-cappella and instrumental. During passive listening to the a-cappella version, a weak left-dominant asymmetry of blood flow acceleration was observed, while there was no hemispheric asymmetry during listening to the instrumental version. During the task of fugue theme recognition, a highly significant asymmetry in favour of the right MCA was observed with both versions. It is concluded that when the processing of complex musical material has to be based on the analysis of melodic contour features and calls for working memory capacities a right hemisphere dominance is observed even in musically sophisticated subjects.

Adult↗
PubMed2000

Characterization of the recombinase activating gene-1 and 2 locus in the Japanese pufferfish, Fugu rubripes.

The recombinase activating genes (RAG1 and RAG2) encode nuclear proteins that directly mediate the mechanism V(D)J recombination process that occurs in T- and B-lymphocytes. The expression of RAG1 and RAG2 is required for the proper development of maturing lymphocytes. To identify evolutionary conserved regulatory regions adjacent to both genes we isolated and sequenced a cosmid clone containing 43kb of genomic DNA of the Japanese pufferfish, Fugu rubripes. Fugu has a haploid genome of 400Mb and contains the same number of genes as the genome of higher vertebrates. With low abundance of repetitive DNA, the genome of the pufferfish has shown to be ideal for comparative genomics. We found three complete genes, RAG1, RAG2 and ACS (a possible homologue of the plant 1-aminocyclopropane-carboxylate synthase gene). There is also the 5' exon of a prohormone convertase gene, possibly PACE4. The genetic structure of both RAG1 and RAG2 is identical to that found in other fish, but the size of the intergenic region is smaller in Fugu. Expression analysis by RT-PCR shows the presence of RAG transcripts in kidney of adult Fugu. The human ACS was identified in a cosmid assigned to chromosome 11p11, which is close to the location of the RAGs (11p12). This indicates conservation of linkage between human and pufferfish.

Animals↗
PubMed2002

The mitochondrial genome of the pufferfish, Fugu rubripes, and ordinal teleostean relationships.

The small nuclear genome of the pufferfish, Fugu rubripes (order Tetraodontiformes), makes this species highly interesting for genome research. In order to establish the phylogenetic position of the Tetraodontiformes relative to other teleostean orders that might also have a reduced nuclear genome size, we have sequenced the mitochondrial (mt) genome of the pufferfish. The gene order, nucleotide composition and evolutionary rate of the mt genome of the fugu correspond to those of other teleosts. This suggests that the evolution of this genome has not been affected by the processes that led to the dramatic reduction of the size of the nuclear genome of the fugu. The phylogenetic analyses, which were based on the concatenated amino acid sequences of twelve protein-coding mt genes, placed the fugu among the percomorphs. The affinities between the Tetraodontiformes and either the Perciformes or the Zeiformes were limited, however. The common notion of a separate euteleostean clade remained unsupported. The analyses did not support the traditional systematic understanding that the Clupeiformes constitute a basal teleostean lineage. In addition the findings strongly suggest that three teleostean orders, the Perciformes, Zeiformes and Scorpaeniformes, are paraphyletic.

Animals↗
PubMed2002

Identification and analysis of additional copies of the platelet-derived growth factor receptor and colony stimulating factor 1 receptor genes in fugu.

The receptors for the platelet-derived growth factor (PDGFRalpha and PDGFRbeta) belong to a subfamily of protein tyrosine kinase receptors that also includes kit and the colony stimulating factor-1 receptor (CSF1R). In mammals, the genes encoding PDGFRalpha and PDGFRbeta are tandemly linked to the kit and CSF1R genes, respectively. Based on the structural similarity and genomic organization of these four genes, it has been suggested that they arose from an ancestral protein tyrosine kinase receptor gene by two rounds of duplication. We have previously cloned the PDGFRbeta and CSF1R genes from the pufferfish, Fugu rubripes, and shown that they are tandemly linked like the mammalian genes [Genome Res. 6 (1996) 1185]. We have now cloned two additional members of this gene family, fPDGFRbeta2 and fCSF1R2 from the fugu and shown that these two genes are also tandemly linked. This indicates that the PDGFRbeta-CSF1R locus has been duplicated in the lineage leading to fugu. The fugu fPDGFRbeta2 and fCSF1R2 genes contain three and one extra introns, respectively, compared with other members of this family. Polymerase chain reaction cloning of a conserved region of PDGFRbeta gene from other ray-finned fishes identified two copies in the zebrafish (order Cypriniformes) and sunfish (order Tetraodontiformes). These results are discussed in the context of the proposed teleost lineage-specific whole genome duplication hypothesis.

Amino Acid Sequence↗
PubMed2001

Conserved synteny between the Fugu and human PTEN locus and the evolutionary conservation of vertebrate PTEN function.

Mutations of PTEN, which encodes a protein-tyrosine and lipid phosphatase, are prevalent in a variety of human cancers. The human genome 'draft' sequence still lacks organization and much of the PTEN and adjacent loci remain undefined. The pufferfish, Fugu rubripes, by virtue of having a compact genome represents an excellent template for rapid vertebrate gene discovery. Sequencing of 56 kb from the Fugu pten (fpten) locus identified four complete genes and one partial gene homologous to human genes. Genes neighboring fpten include a PAPS synthase (fpapss2) differentially expressed between non-metastatic/metastatic human carcinoma cell lines, an inositol phosphatase (fminpp1) and an omega class glutathione-S-transferase (fgsto). We have determined the order of human BAC clones at the hPTEN locus and that the locus contains hPAPSS2 and hMINPP1 genes oriented as are their Fugu orthologs. Although the human genes span 500 kb, the Fugu genes lie within only 22 kb due to the compressed intronic and intergenic regions that typify this genome. Interestingly, and providing striking evidence of regulatory element conservation between widely divergent vertebrate species, the compact 2.1 kb fpten promoter is active in human cells. Also, like hPTEN, fpten has a growth and tumor suppressor activity in human glioblastoma cells, demonstrating conservation of protein function.

Amino Acid Sequence↗
PubMed2002

Conserved regulation of the lymphocyte-specific expression of lck in the Fugu and mammals.

The lck gene encodes a lymphocyte-specific protein-tyrosine kinase that is implicated in T cell maturation and signaling. In mammals, the transcription of the lck gene is regulated by two independent promoters, the proximal promoter, which is active in thymocytes, and the distal promoter, which dominates in mature T cells. In the human and mouse lck gene loci, the two promoter elements are separated by at least 40 kb and 10 kb, respectively. In this study, we have cloned and sequenced 60 kb from the pufferfish (Fugu rubripes) lck locus. The promoter region of the Fugu lck spans only 4.2 kb and contains a proximal and a distal promoter in the 2.3-kb region adjacent to the coding sequence. By generating transgenic mice, we have demonstrated that the compact promoter of the Fugu lck contains regulatory elements that direct expression to lymphoid organs of mice. We were able to localize the regulatory elements to a short region of 830 bp without losing specificity to cultured human T cell line. These results show that the basic mechanisms that mediate lymphocyte-specific expression are conserved between teleosts and mammals. The short promoter of the Fugu lck isolated by us offers a powerful tool for labeling T cells, targeting expression, and manipulating T cell activity in fishes as well as in mammals.

Amino Acid Sequence↗
PubMed1995

Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.

Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.

Animals↗
PubMed2003

Working with Dissociative Fugue in a general psychotherapy practice: a cautionary tale.

Dissociative Fugue is a somewhat rare condition that therapists may see only once or twice over the course of a professional career. A brief review of the uses of hypnosis in the treatment of Dissociative Fugue is followed by a presentation of the case of a 51-year-old man who presented with the clinical picture of Dissociative Fugue State and who experienced complete amnesia for the time prior to the fugue state. This article focuses on the pitfalls that the psychotherapist in a general practice may face when working with such a patient and offers specific recommendations and scripts that may be useful in proceeding with treatment.

Anger↗
PubMed2002

Characterization of the platelet-derived growth factor receptor alpha and c-kit genes in the pufferfish Fugu rubripes.

The receptor tyrosine kinase type III subfamily includes the PDGF receptors (alpha and beta), c-kit and the colony stimulating factor 1 receptor (CSF1R). The similar genomic organization of the genes encoding these receptors and the observation that in mammals, the genes for PDGFR alpha and PDGFR beta are tandemly linked with the c-kit and CSF1R genes, respectively, suggest that these genes arose from an ancestral receptor tyrosine kinase gene. We have previously cloned two copies each of the PDGFR beta and CSF1R genes from the pufferfish, Fugu rubripes, and shown that they are tandemly linked. We have now cloned the Fugu PDGFR alpha and c-kit genes and show that they are also tandemly linked. The intergenic region between the two genes in the Fugu (13 kb) and humans (350 kb) contains a conserved 59 bp element, which may play a role in regulation. The Fugu PDGFR alpha gene is transcribed from two promoters giving rise to alternate transcripts.

Amino Acid Sequence↗
PubMed1996

Conserved linkage between the puffer fish (Fugu rubripes) and human genes for platelet-derived growth factor receptor and macrophage colony-stimulating factor receptor.

We have cloned and sequenced the teleost homologs of the human genes encoding platelet-derived growth factor receptor-beta (PDGFR beta) and macrophage colony-stimulating factor 1 receptor (CSFIR) from the puffer fish Fugu rubripes. The Fugu PDGFR beta and CSFIR genes each consist of 21 coding exons similar to the human CSFI gene, but are considerably smaller than their human counterparts because of the smaller introns. Furthermore, the two Fugu genes are linked tandemly in a head-to-tail array similar to their human homologs with 2.2 kb of intergenic sequence. Amino acid sequences of the Fugu and human PDGFR beta and CSFIR genes show an overall homology of 45% and 39%, respectively, with the kinase domains showing a much higher degree of conservation. Dot-matrix analysis revealed several short stretches of conserved sequences in the 3' untranslated regions of the PDGFR beta genes and the adjacent promoter regions of the CSFIR genes. These conserved sequences may have a role in the regulation of expression of either or both of these closely linked genes.

Amino Acid Sequence↗
PubMed1996

Les Aliénés voyageurs: how fugue became a medical entity.

Dissociative fugue was first treated as a distinct psychiatric illness in Bordeaux in 1887, and was taken up by Charcot as automatisme ambulatoire in 1888. Charcot held that fugue episodes were caused by latent epilepsy; his opponents maintained an hysterical origin. The diagnosis flourished in France for more than a decade but, like the superordinate diagnosis of hysteria, had faded by 1910, although it was exported to Italy, Germany and Russia (but not the anglophone world). It was closely associated with vagrancy as a social problem, and military doctors tried to define the illness in order to protect deserters from punishment. Fugue was a companion to multiple personality, especially in respect of gender - most multiples were women, most fugueurs were men. Dissociative fugue provides a cameo illustration of how a psychiatric entity comes into being and then disappears.

Europe↗
PubMed2004

Duplicated receptors for VIP and PACAP (VPAC1R and PAC1R) in a teleost fish, Fugu rubripes.

Two principal groups of receptors orthologous with human PAC1R and VPAC1R and were identified and characterised at the genomic level in the teleost fish Fugu rubripes. An additional group orthologous with VPAC2R was also identified and partially characterised. In Fugu, gene duplication of each of the PAC1Rs, VPAC1Rs and VPAC2Rs appears to have occurred. The topology of the tree surrounding the Fugu duplications and other isolated piscine sequences indicates that the duplication events for these six genes clearly preceded the speciation event leading to the Cypriniformes and Tetraodontiformes and is probably teleost-specific. Overall, the combined pattern of gene expression for each pair of duplicated genes mirrored the expression in other vertebrates. However, within each pair of duplicates further specialisation had occurred, with each demonstrating differential tissue distribution profiles suggesting they that may be responsible for the divergent action of the ligands, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP). The Fugu VPAC1R gene regions showed conserved synteny with human chromosome 3p21.3 and also C. elegans chromosome X, indicating that the putative ancestral human chromosome 3 region may be equivalent to chromosome X in Caenorhabditis elegans.

Amino Acid Sequence↗
PubMed1999

Psychogenic or dissociative fugue: a clinical investigation of five cases.

Dissociative fugue (formerly psychogenic fugue) is a rare and little understood dissociative disorder. Following a review of the pertinent literature, five cases of dissociative fugue are described. These cases were systematically studied with a comprehensive history, mental status examination, physical and neurological evaluation, review of previous medical and psychiatric records, and psychological testing including MMPI, WAIS-R, electroencephalogram, and Dissociative Experiences Scale. An unexpected finding was that, in some cases, associated criminal activity may allow the person with dissociative fugue to continue to function in spite of their loss of memory and original identity.

Adult↗