Publications (17)51.22 Total impact
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Article: Genetic, comparative genomic, and expression analyses of the Mc1r locus in the polychromatic Midas cichlid fish (Teleostei, Cichlidae Amphilophus sp.) species group.
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ABSTRACT: Natural populations of the Midas cichlid species in several different crater lakes in Nicaragua exhibit a conspicuous color polymorphism. Most individuals are dark and the remaining have a gold coloration. The color morphs mate assortatively and sympatric population differentiation has been shown based on neutral molecular data. We investigated the color polymorphism using segregation analysis and a candidate gene approach. The segregation patterns observed in a mapping cross between a gold and a dark individual were consistent with a single dominant gene as a cause of the gold phenotype. This suggests that a simple genetic architecture underlies some of the speciation events in the Midas cichlids. We compared the expression levels of several candidate color genes Mc1r, Ednrb1, Slc45a2, and Tfap1a between the color morphs. Mc1r was found to be up regulated in the gold morph. Given its widespread association in color evolution and role on melanin synthesis, the Mc1r locus was further investigated using sequences derived from a genomic library. Comparative analysis revealed conserved synteny in relation to the majority of teleosts and highlighted several previously unidentified conserved non-coding elements (CNEs) in the upstream and downstream regions in the vicinity of Mc1r. The identification of the CNEs regions allowed the comparison of sequences from gold and dark specimens of natural populations. No polymorphisms were found between in the population sample and Mc1r showed no linkage to the gold phenotype in the mapping cross, demonstrating that it is not causally related to the color polymorphism in the Midas cichlid.Journal of Molecular Evolution 05/2010; 70(5):405-12. · 2.27 Impact Factor -
Article: Dual control by a single gene of secondary sexual characters and mating preferences in medaka.
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ABSTRACT: Animals utilize a wide variety of tactics to attract reproductive partners. Behavioral experiments often indicate an important role for visual cues in fish, but their molecular basis remains almost entirely unknown. Studies on model species (such as zebrafish and medaka) allow investigations into this fundamental question in behavioral and evolutionary biology. Through mate-choice experiences using several laboratory strains of various body colors, we successfully identified one medaka mutant (color interfere; ci) that is distinctly unattractive to reproductive partners. This unattractiveness seems to be due to reduced orange pigment cells (xanthophores) in the skin. The ci strain carries a mutation on the somatolactin alpha (SLa) gene, therefore we expected over-expression of SLa to make medaka hyper-attractive. Indeed, extremely strong mating preferences were detected in a choice between the ci and SLa-transgenic (Actb-SLa:GFP) medaka. Intriguingly, however, the strains showed opposite biases; that is, the mutant and transgenic medaka liked to mate with partners from their own strain, similar to becoming sexually isolated. This study spotlighted SLa as a novel mate-choice gene in fish. In addition, these results are the first demonstration of a single gene that can pleiotropically and harmoniously change both secondary sexual characters and mating preferences. Although theoretical models have long suggested joint evolution of linked genes on a chromosome, a mutation on a gene-regulatory region (that is, switching on/off of a single gene) might be sufficient to trigger two 'runaway' processes in different directions to promote (sympatric) speciation.BMC Biology 09/2009; 7:64. · 5.75 Impact Factor -
Article: Effects of constitutive expression of somatolactin alpha on skin pigmentation in medaka.
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ABSTRACT: Somatolactin alpha (SLa) is a fish-specific peptide hormone secreted from the pituitary. Its functions have been investigated for the last decade but are still under debate. We previously reported a frame-shift mutation on SLa in a medaka mutant, color interfere (ci), which shows defects in body-color regulation, lipid storage, and cortisol secretion. In this study, we examined the effects of introducing a DNA fragment which constitutively expresses wild-type SLa under regulation of the beta-actin (Actb) promoter into the ci genome. We successfully visualized the transgene expression by taking advantage of an internal ribosome entry site (IRES) and the green fluorescent protein (GFP). The transgenic medaka, Actb-SLa:GFP, exhibited a reversed body-color phenotype of ci; more orange xanthophores and less white leucophores. We also detected more black melanophores and less silver iridophores, which indicates SLa's comprehensive role in regulating all types of pigment cells in the skin. Unexpectedly, the defects in lipid/cortisol contents remained in Actb-SLa:GFP. Therefore, the causal relationship between SLa and lipid/cortisol metabolisms relapses to an open question which needs to be reassessed by other types of experiments. Both the Actb-SLa:GFP and ci fish grow and mature similar to wild type, indicating SLa contributes little to growth regulation in spite of the fact that it binds to a teleost-specific paralog of growth-hormone receptor in vitro. The present study provides definitive evidence for SLa's principal and indispensable role in body-color regulation in medaka.Gene 05/2009; 442(1-2):81-7. · 2.34 Impact Factor -
Article: A microsatellite-based genetic linkage map of the cichlid fish, Astatotilapia burtoni (Teleostei): a comparison of genomic architectures among rapidly speciating cichlids.
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ABSTRACT: Cichlid fishes compose an astonishingly large number of species and formed species flocks in record-breaking time. To facilitate efficient genome scans and comparisons of cichlid genomes, we constructed a medium-density genetic linkage map of microsatellite markers of Astatotilapia burtoni. The mapping cross was derived from two inbred laboratory lines to obtain F(2) progeny by intercrossing. The map revealed 25 linkage groups spanning 1249.3 cM of the genome (size approximately 950 Mb) with an average marker spacing of 6.12 cM. The seven Hox clusters, ParaHox C1, and two paralogs of Pdgfrbeta were mapped to different linkage groups, thus supporting the hypothesis of a teleost-specific genome duplication. The A. burtoni linkage map was compared to the other two available maps for cichlids using shared markers that showed conservation and synteny among East African cichlid genomes. Interesting candidate genes for cichlid speciation were mapped using SNP markers.Genetics 09/2008; 182(1):387-97. · 4.01 Impact Factor -
Article: Rescue from oculocutaneous albinism type 4 using medaka slc45a2 cDNA driven by its own promoter.
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ABSTRACT: Patients and vertebrate mutants with oculocutaneous albinism type 4 (OCA4) have mutations in the solute carrier family 45 member 2 (slc45a2) gene. However, there is no empirical evidence for this gene-phenotype relationship. There is a unique OCA4 mutant in medaka (b) that exhibits albinism only in the skin, but the mechanism underlying this phenotype is also unknown. In this study, we rescued medaka OCA4 phenotypes, in both the eyes and the skin, by micro-injection of an slc45a2-containing genomic fragment or slc45a2 cDNA driven by its own 0.9-kb promoter. We also identified a spontaneous nucleotide change of 339 bp in the promoter as the b mutation. There are multiple transcription start sites in medaka slc45a2, as in its human ortholog, and only the shortest and eye-specific mRNA is transcribed with the b mutation. Interestingly, we further revealed a conserved pyrimidine (Py)-rich sequence of approximately 10 bp in the promoter by medaka-pufferfish comparative genomics and verified that it plays an indispensable role for expression of slc45a2 in the skin. Further studies of the 0.9-kb promoter identified in this study should provide insights into the cis/trans-regulatory mechanisms underlying the ocular and cutaneous expression of slc45a2.Genetics 03/2008; 178(2):761-9. · 4.01 Impact Factor -
Article: Evolution of receptors for growth hormone and somatolactin in fish and land vertebrates: lessons from the lungfish and sturgeon orthologues.
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ABSTRACT: Two cognate hormones, growth hormone (GH) and somatolactin (SL), control several important physiological processes in vertebrates. Knowledge about GH and its receptor (GHR) has accumulated over the last decades. However, much less is known about SL and its receptor (SLR). SL is found only in fish (including lungfish), suggesting that it was present in the common ancestor of vertebrates, but was lost secondarily in the lineage leading to land vertebrates after the lungfish branched off. SLR was suggested to be a duplicated copy of GHR acquired only in teleosts via the fish-specific genome duplication (FSGD). This scenario (i.e., the existence of SL but not SLR in the vertebrate ancestors) is intriguing but contested. In this study, we first evaluated the plausibility of this scenario through synteny analyses and found that the loci for GHR and SLR are located in syntenic genomic positions, whereas the loci for GH and SL are not. Next, we cloned GHRs of lungfish and sturgeon, which possess SL but did not undergo the FSGD (i.e., they should not possess SLR). Their phylogenetic positions in the GHR/SLR gene tree further support the fish-specific scenario for the GHR-SLR duplication. Interestingly, their sequences share greater similarity with teleost SLRs and reptilian/amphibian GHRs than with the GHRs of mammals, birds, and teleosts. On the basis of these results, we discuss the validity of the nomenclature of the teleost-specific copy of GHR as SLR and an ancestral receptor(s) for SL before the evolution of SLR during the FSGD.Journal of Molecular Evolution 11/2007; 65(4):359-72. · 2.27 Impact Factor -
Article: Reduced expression of vps11 causes less pigmentation in medaka, Oryzias latipes.
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ABSTRACT: In this article, we describe the medaka mutant pale gray eyes (pge) that shows reduction of black, white, and silver pigmentation and lethality approximately a week after hatching. The pge mutation was mapped to the tip of linkage group 14 and no recombinations were observed between the mutation and medaka vps11 in 900 meioses. Vps 11 is one of the evolutionarily conserved class C vacuolar protein sorting genes (c-vps: vps11, vps16, vps18, and vps33), whose products physically associate to form the c-vps protein complex required for vesicle docking and fusion in the budding yeast. Mutations in vps16, vps18, and vps33 are known to result in decreased pigmentation in organisms such as Drosophila. We cloned the full-length medaka vps11 cDNA by rapid amplification of cDNA ends (RACE) and found no RACE products from the pge mutants. Similarly, no vps11 transcripts were detected from the pge mutants by Northern analysis. The injection of an antisense morpholino against vps11 phenocopied the pge mutant. Taken together, the results suggest that reduced expression of medaka vps11 causes pge and that medaka vps11 is indispensable for survival and normal pigmentation.Pigment Cell Research 01/2007; 19(6):628-34. · 4.29 Impact Factor -
Article: Effects of acid water exposure on plasma cortisol, ion balance, and immune functions in the "cobalt" variant of rainbow trout.
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ABSTRACT: This study was undertaken to examine physiological responses to acidification of environmental water in the "cobalt" variant of rainbow trout (Oncorhynchus mykiss), which exhibits malformation of the pituitary, by following changes in plasma levels of cortisol and electrolytes, blood pH, gill Na(+), K(+)-ATPase activity, and immune functions after exposure to acid water (pH 4.5). Resting levels of plasma cortisol and lysozyme were significantly lower in the cobalt variant than in the normal trout, whereas plasma ceruloplasmin was significantly higher in the cobalt variant, suggesting that some endocrine factors, lacking or deficient in the cobalt variant, are important for the regulation of its immune functions. Blood pH was slightly but significantly lower in the cobalt variant at rest. After exposure to acid water for 24 h, both the normal trout and cobalt variant showed a significant elevation in plasma cortisol, although the increased level in the cobalt variant was still lower than that in the normal trout transferred to neutral water. No differences were seen in blood pH, plasma electrolytes, and gill Na(+), K(+)-ATPase activity between the normal trout and the cobalt variant, indicating that the cobalt variant regulates ion balance when exposed to acid water, despite malformation of the pituitary. Although the normal trout showed a reduction in plasma lysozyme level after acid exposure, there was no significant change in the cobalt trout. Adverse effects of pituitary malformation on ion balance and immune functions may be compensated by extrapituitary factors in the cobalt variant when it is exposed to acid water.ZOOLOGICAL SCIENCE 09/2006; 23(8):707-13. · 0.95 Impact Factor -
Article: Functional characterization of visual opsin repertoire in Medaka (Oryzias latipes).
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ABSTRACT: A variety of visual pigment repertoires present in fish species is believed due to the great variation under the water of light environment. A complete set of visual opsin genes has been isolated and characterized for absorption spectra and expression in the retina only in zebrafish. Medaka (Oryzias latipes) is a fish species phylogenetically distant from zebrafish and has served as an important vertebrate model system in molecular and developmental genetics. We previously isolated a medaka rod opsin gene (RH1). In the present study we isolated all the cone opsin genes of medaka by genome screening of a lambda-phage and bacterial artificial chromosome (BAC) libraries. The medaka genome contains two red, LWS-A and LWS-B, three green, RH2-A, RH2-B and RH2-C, and two blue, SWS2-A and SWS2-B, subtype opsin genes as well as a single-copy of the ultraviolet, SWS1, opsin gene. Previously only one gene was believed present for each opsin type as reported in a cDNA-based study. These subtype opsin genes are closely linked and must be the products of local gene duplications but not of a genome-wide duplication. Peak absorption spectra (lambda(max)) of the reconstituted photopigments with 11-cis retinal varied greatly among the three green opsins, 452 nm for RH2-A, 516 nm for RH2-B and 492 nm for RH2-C, and between the two blue opsins, 439 nm for SWS2-A and 405 nm for SWS2-B. Zebrafish also has multiple opsin subtypes, but phylogenetic analysis revealed that medaka and zebrafish gained the subtype opsins independently. The lambda and BAC DNA clones isolated in this study could be useful for investigating the regulatory mechanisms and evolutionary diversity of fish opsin genes.Gene 05/2006; 371(2):268-78. · 2.34 Impact Factor -
Article: Medaka double mutants for color interfere and leucophore free: characterization of the xanthophore-somatolactin relationship using the leucophore free gene.
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ABSTRACT: Somatolactin (SL) plays an essential role in body-color regulation in medaka and is encoded by the color interfere (ci) locus. The ci mutant fish possess constitutively increased numbers of leucophores and a concomitant decrease in visible xanthophores. However, the mechanism of action of SL on these cell types, and the role of SL in body-color regulation in other species, is unknown. In this study, we verified an SL-xanthophore relationship in ci mutant fish using the leucophore free (lf) gene. Histological observation of lf larvae indicated that these mutants do not possess differentiated leucophores. The ci-lf double mutant, whose genotype was confirmed using DNA markers, lacked leucophores; however, the number of xanthophores remained low, demonstrating that leucophores are not necessary for mediating SL signaling to xanthophores. This finding suggests a conserved function for SL in xanthophore regulation across species, rather than the evolution of a medaka-specific and leucophore-dependent role of SL in body-color regulation. Our results also demonstrate that the lf gene has an indispensable role in leucophore development epistatic to SL signaling. The lf gene has not been cloned. The high-resolution recombination map surrounding the lf locus constructed in this study, together with medaka whole genome sequences that will be released soon, will allow the rapid cloning of the lf gene by forward genetic approaches.Archiv für Entwickelungsmechanik der Organismen 04/2006; 216(3):152-7. · 1.77 Impact Factor -
Article: Medaka receptors for somatolactin and growth hormone: phylogenetic paradox among fish growth hormone receptors.
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ABSTRACT: Somatolactin (SL) in fish belongs to the growth hormone/prolactin family. Its ortholog in tetrapods has not been identified and its function(s) remains largely unknown. The SL-deficient mutant of medaka (color interfere, ci) and an SL receptor (SLR) recently identified in salmon provide a fascinating field for investigating SL's function(s) in vivo. Here we isolated a medaka ortholog of the salmon SLR. The mRNA is transcribed in variable organs. Triglycerides and cholesterol contents in the ci are significantly higher than those in the wild type, providing the first evidence of SL's function in suppressing lipid accumulation to organs. Interestingly, phylogenetic comparisons between the medaka SLR and growth hormone receptor (GHR), which is also isolated in this study, in relation to GHRs of other fish, suggested that all GHRs reported from nonsalmonid species are, at least phylogenetically, SLRs. An extra intron inserted in medaka and pufferfish SLRs and flounder and sea bream GHRs also supports their orthologous relationship, but not with tetrapod GHRs. These results may indicate lineage-specific diversification of SLR and GHR functions among fish or just an inappropriate naming of these receptors. Further functional and comparative reassessments are necessary to address this question.Genetics 01/2006; 171(4):1875-83. · 4.01 Impact Factor -
Article: Conserved function of medaka pink-eyed dilution in melanin synthesis and its divergent transcriptional regulation in gonads among vertebrates.
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ABSTRACT: Medaka is emerging as a model organism for the study of vertebrate development and genetics, and its effectiveness in forward genetics should prove equal to that of zebrafish. Here, we identify by positional cloning a gene responsible for the medaka i-3 albino mutant. i-3 larvae have weakly tyrosinase-positive cells but lack strongly positive and dendritic cells, suggesting loss of fully differentiated melanophores. The region surrounding the i-3 locus is syntenic to human 19p13, but a BAC clone covering the i-3 locus contained orthologs located at 15q11-13, including OCA2 (P). Medaka P consists of 842 amino acids and shares approximately 65% identity with mammalian P proteins. The i-3 mutation is a four-base deletion in exon 13, which causes a frameshift and truncation of the protein. We detected medaka P transcripts in melanin-producing eyeballs and (putative) skin melanophores on embryos and an alternatively spliced form in the non-melanin-producing ovary or oocytes. The mouse p is similarly expressed in gonads, but not alternatively spliced. This is the first isolation of nonmammalian P, the functional mechanism of action of which has not yet been elucidated, even in mammals. Further investigation of the functions of P proteins and the regulation of their expression will provide new insight into body color determination and gene evolution.Genetics 12/2004; 168(3):1519-27. · 4.01 Impact Factor -
Article: Somatolactin selectively regulates proliferation and morphogenesis of neural-crest derived pigment cells in medaka.
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ABSTRACT: Species-specific colors and patterns on animal body surfaces are determined primarily by neural-crest-derived pigment cells in the skin (chromatophores). However, even closely related species display widely differing patterns. These contrasting aspects of chromatophores (i.e., the fixed developmental control within species and extreme diversity among species) seem to be a curious and suitable subject for understanding evolution and diversity of organisms. Here we identify a gene responsible for medaka "color interfere" mutants by positional cloning. These mutants do not show any obvious morphological and physiological defects other than defects in chromatophore proliferation and morphogenesis. The mutation has been identified as an 11-base deletion in somatolactin, which causes truncation 91 aa upstream of the C terminus of the protein's 230 aa. Somatolactin transcription changed dramatically during morphological body color adaptation to different backgrounds. This genetic evidence explains somatolactin function. Studying this mutant will provide further insights into the development and regulation of chromatophores and clues for reassessing other functions of somatolactin suggested in other fish.Proceedings of the National Academy of Sciences 08/2004; 101(29):10661-6. · 9.68 Impact Factor -
Article: Induction and characterization of mutations at the b locus of the medaka, Oryzias latipes.
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ABSTRACT: The b locus is one of the most familiar pigmentation loci in the medaka, but its biochemical function is still unknown. Here we report induction of new mutations at the b locus by radiation and ENU. We also characterized all these mutations and previously isolated spontaneous ones on the phenotypic basis. Unexpectively, all the 18 induced mutations reduced melanin contents in both eyes and skin correlatively, although degree of reduction was varied from mutations to mutations. Moreover, presumed null mutants (bs8, bg8, bc2, bd3, bd6, bg13, bg19, bg24) had slightly melanized (dark red) eyes. These results suggest that the b-locus product plays an important but not a critical role in melanogenesis. The spontaneous mutants were divided into two types: one (bdl2, bdl3, and bp) had similarities with the induced mutants in that they had slightly colored eyes and skin, the other (bv, B', bd, bdl1, and b) exhibited normally black eyes but lightly colored skin. The present study supports our recent results (Fukamachi et al., 2001) that mutational changes were found in the coding region of the b gene in some of the mutants which reduced both eyes and skin melanogenesis, while the mutational change for the b allele could not be found there. We speculate that the bv, B', bd, bdl1, and b alleles might arise by the mutations in the regulatory region for skin melanogenesis.ZOOLOGICAL SCIENCE 05/2002; 19(4):411-7. · 0.95 Impact Factor -
Article: Distinctive distribution of AIM1 polymorphism among major human populations with different skin color.
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ABSTRACT: The genetic background for human skin color has been a major topic in human genetics; however, its molecular basis is still unclear. The gene for the AIM-1 protein (AIM1) was recently found to be responsible for the body color of medaka fish. In the search for the genes controlling human skin color variations, we have investigated genetic polymorphisms of this gene, and we have found a single-nucleotide polymorphism that has clear association with major human populations in terms of skin color.Journal of Human Genetics 02/2002; 47(2):92-4. · 2.57 Impact Factor -
Article: A Microsatellite-Based Genetic Linkage Map of the Cichlid Fish, Astatotilapia bunoni (Teleostei) : a Comparison of GenomicArchitectures Among Rapidly Speciating Cichlids
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ABSTRACT: Cichlid fishes compose an astonishingly large number of species and fonned species flocks in recordbreaking time. To facilitate efficient genome scans and comparisons of cichlid genomes, we constructed a medium-density genetic linkage map of microsatellite markers of Astaloliklpia burloni. The mapping cross was derived from two inbred laboratory lines to obtain F2 progeny by intercrossing. The map revealed 25 linkage groups spanning 1249.3 cM of the genome (size ~950 Mb) with an average marker spacing of6.12 cM. The seven Hox clusters, ParaHox Cl, and two paralogs of Pdgfrf!> were mapped to different linkage groups, thus supporting the hypothesis of a teleost-specific genome duplication. The A. burloni linkage map was compared to the other two available maps for cichlids using shared markers that showed conservation and synteny among East African cichlid genomes. Interesting candidate genes for cichlid speciation were mapped using SNP markers.First publ. in: Genetics 182 (2009), pp. 387-397. -
Article: Genomic analysis of γ-ray-induced germ-cell mutations at the b locus recovered from the medaka specific-locus test
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ABSTRACT: To study how γ-ray-induced germ-cell mutations are fixed at the early embryonic stage of the next generation, genomic alterations in the b locus mutants (colorless melanophores) detected during development in the medaka specific-locus test (SLT) were analyzed. First, nine anonymous DNA markers linked to the b locus were cloned and mapped into the region extending about 47 cM surrounding the b locus. Next, losses of paternal alleles of these DNA markers were examined in each of the 51 γ-ray-induced b locus mutants obtained after irradiation of sperm or spermatids. In these mutants, 47 were dominant lethals, three were semi-viable and one was viable. All the mutants examined had large deletions surrounding the b locus. One viable mutant had an interstitial deletion, while all the semi-viable and dominant lethal ones appeared to have terminal deletions. Deletions extending about 20–35 cM were the most frequently observed in 18 of the 51 mutants examined. The largest one extended more than 40 cM. These results suggest that most of the γ-ray induced germ cell mutations recovered as total specific-locus mutants were accompanied by large genomic deletions, which eventually led the mutant embryos to dominant lethality.Mutation Research/Mutation Research Genomics.
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Institutions
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2007–2010
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Universität Konstanz
- Department of Biology
Konstanz, Baden-Wuerttemberg, Germany
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2004–2008
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The University of Tokyo
- Department of Integrated Biosciences
Tokyo, Tokyo-to, Japan
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