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Shuichi Hiraoka

Publications and source records attributed to Shuichi Hiraoka.

17 recordsLinked to original sources
PubMed2006

Electrostatically controlled hierarchical arrangement of monocationic silver(I) and dicationic mercury(II) ions between disk-shaped template ligands.

This paper describes hierarchical arrangement of three Ag+ and three Hg2+ ions using two disk-shaped hexa-monodentate template ligands in which three oxazolyl rings are arranged each on the two concentric circles. The hierarchical manner of ligand arrangement allows the selective binding of monocationic Ag+ and dicationic Hg2+ ions to the inner first and the outer second generation coordination sites, respectively. This hierarchically well-balanced metal assembly should arise primarily from a minimized electrostatic repulsion between positively charged six metal ions arranged within the heteronuclear complex.

Journal Article↗
PubMed2006

Fluvoxamine, a selective serotonin reuptake inhibitor, and 5-HT2C receptor inactivation induce appetite-suppressing effects in mice via 5-HT1B receptors.

Serotonin (5-hydroxytryptamine; 5-HT) 2C receptors and the downstream melanocortin pathway are suggested to mediate the appetite-suppressing effects of 5-HT drugs such as m-chlorophenylpiperazine (mCPP) and fenfluramine. Here, we report that fluvoxamine (3-30 mg/kg), a selective serotonin reuptake inhibitor (SSRI), in the presence of SB 242084 (1-2 mg/kg), a selective 5-HT2C receptor antagonist, exerts appetite-suppressing effects while fluvoxamine or SB 242084 alone has no effect. The appetite-suppressing effects were attenuated in the presence of SB 224289 (5 mg/kg), a selective 5-HT1B receptor antagonist. Moreover, CP 94253 (5-10 mg/kg), a selective 5-HT1B receptor agonist, exerted appetite-suppressing effects and significantly increased hypothalamic pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) gene expression and decreased hypothalamic orexin gene expression. These results suggest that fluvoxamine and inactivation of 5-HT2C receptors exert feeding suppression through activation of 5-HT1B receptors, and that 5-HT1B receptors up-regulate hypothalamic POMC and CART gene expression and down-regulate hypothalamic orexin gene expression in mice.

Analysis of Variance↗
PubMed2005

Presenilin-1 controls the growth and differentiation of endothelial progenitor cells through its beta-catenin-binding region.

Presenilin-1 (PS1) is a gene responsible for the development of early-onset familial Alzheimer's disease. Targeted disruption of the PS1 gene in mice suggested that PS1 might be involved in angiogenesis. We have used an in vitro embryonic stem (ES) cell culture system to prepare endothelial progenitor cells (EPC) lacking PS1 and investigated the roles of PS1 in endothelial cell lineage. With this system, Flk-1+ E-cadherin- EPC were generated from PS1-deficient ES cells, and the EPC lacking PS1 as well as wild-type EPC grew to form VE-cadherin+ endothelial colonies supported by a layer of OP9 stromal cells. Although the endothelial colonies from PS1-deficient EPC showed morphology similar to those from wild-type EPC, the PS1-deficient EPC formed a large number of the colonies compared to wild-type EPC. The enhanced colony-forming ability of PS1-deficient EPC was attenuated by the inductions of wild-type human PS1. To differentiate multiple activities of PS1 for colony-forming ability, we used two types of human PS1 mutants: one (hPS1D257A) with the aspartate to alanine mutation at residue 257 that impairs the proteolytic activity of PS1, and the other (hPS1Deltacat) deleting amino acids 340-371 of the cytosolic loop sequence essential for beta-catenin binding. hPS1D257A showed activity to regulate the colony-forming ability of PS1-deficient EPC, while hPS1Deltacat failed to exhibit this activity. These results suggest that PS1 regulates the growth and differentiation of endothelial progenitor cells through its beta-catenin-binding region and that the defect of PS1 function in endothelial cell lineage could contribute to the induction of vascular pathology.

Animals↗
PubMed2005

Differential contributions of Mesp1 and Mesp2 to the epithelialization and rostro-caudal patterning of somites.

Mesp1 and Mesp2 are homologous basic helix-loop-helix (bHLH) transcription factors that are co-expressed in the anterior presomitic mesoderm (PSM) just prior to somite formation. Analysis of possible functional redundancy of Mesp1 and Mesp2 has been prevented by the early developmental arrest of Mesp1/Mesp2 double-null embryos. Here we performed chimera analysis, using either Mesp2-null cells or Mesp1/Mesp2 double-null cells, to clarify (1) possible functional redundancy and the relative contributions of both Mesp1 and Mesp2 to somitogenesis and (2) the level of cell autonomy of Mesp functions for several aspects of somitogenesis. Both Mesp2-null and Mesp1/Mesp2 double-null cells failed to form initial segment borders or to acquire rostral properties, confirming that the contribution of Mesp1 is minor during these events. By contrast, Mesp1/Mesp2 double-null cells contributed to neither epithelial somite nor dermomyotome formation, whereas Mesp2-null cells partially contributed to incomplete somites and the dermomyotome. This indicates that Mesp1 has a significant role in the epithelialization of somitic mesoderm. We found that the roles of the Mesp genes in epithelialization and in the establishment of rostral properties are cell autonomous. However, we also show that epithelial somite formation, with normal rostro-caudal patterning, by wild-type cells was severely disrupted by the presence of Mesp mutant cells, demonstrating non-cell autonomous effects and supporting our previous hypothesis that Mesp2 is responsible for the rostro-caudal patterning process itself in the anterior PSM, via cellular interaction.

Animals↗
PubMed2004

Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries.

We have been conducting a mouse cDNA project to predict protein-coding sequences of mouse homologues of human KIAA and FLJ genes since 2001. As an extension of these projects, we herein present the entire sequences of 500 mKIAA cDNA clones and 4 novel cDNA clones that were incidentally identified during this project. We have isolated cDNA clones from the size-fractionated mouse cDNA libraries derived from 7 tissues and 3 types of cultured cells. The average size of the 504 cDNA sequences reached 4.3 kb and that of the deduced amino acid sequences from these cDNAs was 807 amino acid residues. We assigned the integrity of CDSs from the comparison with the corresponding human KIAA cDNA sequences. The comparison of mouse and human sequences revealed that two different human KIAA cDNAs are derived from single genes. Furthermore, 3 out of 4 proteins encoded in the novel cDNA clones showed moderate sequence similarity with human KIAA proteins, thus we could obtain new members of KIAA protein families through our mouse cDNA projects.

Animals↗
PubMed2004

Prediction of the coding sequences of mouse homologues of FLJ genes: the complete nucleotide sequences of 110 mouse FLJ-homologous cDnas identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries.

We have been conducting a mouse cDNA project to predict protein-coding sequences of mouse KIAA-homologous genes since 2001. As an extension of this project, we also started to accumulate mouse cDNA clones homologous to the human FLJ cDNA clones which are another long cDNA resource produced in our institute. We have isolated the cDNA clones from size-fractionated cDNA libraries derived from five different mouse tissues and natural killer T-cells. Although the human FLJ cDNA clones were originally derived from human spleen libraries, one-third of their mouse homologues were obtained from the brain library. We designated these homologues "mFLJ" plus a 5-digit number and herein characterized 110 mFLJ cDNA clones. We assigned an integrity of the CDSs from the comparison of the 110 cDNA clones with the corresponding human FLJ cDNA clones. The average size of the 110 mouse cDNA sequences was 3.8 kb and that of the deduced amino acid sequences from their longest CDS in each cDNA was 663 amino acid residues. Homology and/or motif search against public databases revealed new domains and/or motifs in 26 mFLJ gene products which provide additional speculation regarding the function of FLJ genes.

Animals↗
PubMed2004

Heterotopic assemblage of two different disk-shaped ligands through trinuclear silver(I) complexation: ligand exchange-driven molecular motion.

The sandwich-shaped heterotopic trinuclear Ag+ complex Ag(3)1.2 was exclusively formed from two different tris(thiazolyl) and hexa(thiazolyl) disk-shaped ligands, 1 and 2, with the aid of three Ag+ ions. The variable-temperature 1H NMR study on its complexation behavior revealed that metal-ligand exchanges between the two neighboring thiazolyl nitrogen donors of 2 take place at the three Ag+ centers in concert. DeltaH++ and DeltaS++ for the exchange process were calculated to be 50.5 kJ mol(-1) and -26.7 J mol(-1) K(-1), respectively, and its energy barrier at 298 K was estimated to be 58.5 kJ mol(-1). Each concerted metal-ligand exchange leads to an intramolecular 60 degrees-rotational motion ((P) <==>(M) conversion) between the two disk-shaped ligands.

Journal Article↗
PubMed2003

Differential regulation by stimulants of neocortical expression of mrt1, arc, and homer1a mRNA in the rats treated with repeated methamphetamine.

The present work was conducted to obtain clues for the possible roles of a novel stimulant-inducible gene mrt1 (methamphetamine-responsive transcript 1) encoding a PDZ-PX protein in stimulant-induced behavioral sensitization. In the young adult rats, repeated daily treatment with methamphetamine (4 mg/kg, intraperitoneally, once a day) for 5 days caused an enhanced behavioral response to methamphetamine: behavioral sensitization. The 5-day intermittent administration of MAP upregulated the basal expression of mrt1 transcripts and eliminated the increasing effects of a challenge dose of MAP (1.6 mg/kg, i.p.) or cocaine (30 mg/kg, i.p.) on mrt1 expression on day 14 of withdrawal in the neocortex that has been considered to be composed of a neuron circuit implicated in the sensitization phenomenon. In contrast, the basal expression of other stimulant-inducible and plasticity-related genes arc and homer1a and the ability of MAP or cocaine challenge to augment the amounts of their transcripts were not affected by the repeated MAP regimen in the cortical area. These findings suggest the differential regulation by stimulant of neocortical mrt1, arc, and homer1a expression in the behaviorally sensitized animals and supports the view that stimulant induction of mrt1 may be involved in the early molecular signalings for stimulant sensitization.

Animals↗
PubMed2003

Prediction of the coding sequences of mouse homologues of KIAA gene: III. the complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries.

We have conducted a human cDNA project to predict protein-coding sequences (CDSs) in large cDNAs (> 4 kb) since 1994, and the number of newly identified genes, known as KIAA genes, already exceeds 2000. The ultimate goal of this project is to clarify the physiological functions of the proteins encoded by KIAA genes. To this end, the project has recently been expanded to include isolation and characterization of mouse KIAA-counterpart genes. We herein present the entire sequences and the chromosome loci of 500 mKIAA cDNA clones and 13 novel cDNA clones that were incidentally identified during this project. The average size of the 513 cDNA sequences reached 4.3 kb and that of the deduced amino acid sequences from these cDNAs was 816 amino acid residues. By comparison of the predicted CDSs between mouse and human KIAAs, 12 mKIAA cDNA clones were assumed to be differently spliced isoforms of the human cDNA clones. The comparison of mouse and human sequences also revealed that four pairs of human KIAA cDNAs are derived from single genes. Notably, a homology search against the public database indicated that 4 out of 13 novel cDNA clones were homologous to the disease-related genes.

Animals↗
PubMed2003

Artificial nucleosides possessing metal binding sites at the 3'- and 5'-positions of the deoxyribose moieties.

This paper describes a convenient synthetic procedure for nucleoside mimics, 1-6, in which the 3',5'-hydroxy groups of natural 2'-deoxythymidine or 2'-deoxyadenosine are replaced by thiol, amine, or alkylthiol groups. Such nucleosides would be built up into a single DNA strand with cooperative participation of metal coordination, where internucleoside linkages are replaced by metal complexation motifs. The X-ray crystal structure and complexation behaviors of 3',5'-dithiothymidine, 1, with Au(I) are also reported.

Alkenes↗
PubMed2002

Syntheses and structure-activity relationships of nonnatural beta-C-nucleoside 5'-triphosphates bearing an aromatic nucleobase with phenolic hydroxy groups: inhibitory activities against DNA polymerases.

Five nonnatural beta-C-nucleoside 5'-triphosphates bearing a 3,4-dihydroxyphenyl (1TP), a 2-hydroxyphenyl (2TP), a 3-hydroxyphenyl (3TP), a 4-hydroxyphenyl (4TP), or a phenyl (5TP) group were synthesized, and their structure-activity relationships were examined for a series of DNA polymerase reactions in vitro under typical polymerase chain reaction conditions. We found that the 5'-triphosphates (1TP-5TP) are not incorporated into DNA strands but inhibit the DNA polymerase reactions in the presence of natural nucleoside 5'-triphosphates (dNTPs). 1TP having two phenolic hydroxy groups at the nucleobase moiety showed the most potent inhibitory effect against DNA synthesis by Ex Taq polymerase (IC(50) = 30 microM). The competition assay indicated that 1TP and dNTPs are most likely to affect DNA polymerase reactions competitively. This finding may raise the appealing possibility that artificial nucleoside 5'-triphosphates having phenolic hydroxy groups could exhibit potent inhibitory activity against DNA-directed enzymatic reactions.

DNA-Directed DNA Polymerase↗
PubMed2002

Characterization of size-fractionated cDNA libraries generated by the in vitro recombination-assisted method.

We here modified a previously reported method for the construction of cDNA libraries by employing an in vitro recombination reaction to make it more suitable for comprehensive cDNA analysis. For the evaluation of the modified method, sets of size-selected cDNA libraries of four different mouse tissues and human brain were constructed and characterized. Clustering analysis of the 3' end sequence data of the mouse cDNA libraries indicated that each of the size-fractionated libraries was complex enough for comprehensive cDNA analysis and that the occurrence rates of unidentified cDNAs varied considerably depending on their size and on the tissue source. In addition, the end sequence data of human brain cDNAs thus generated showed that this method decreased the occurrence rates of chimeric clones by more than fivefold compared to conventional ligation-assisted methods when the cDNAs were larger than 5 kb. To further evaluate this method, we entirely sequenced 13 human unidentified cDNAs, named KIAA1990-KIAA2002, and characterized them in terms of the predicted protein sequences and their expression profiles. Taking all these results together, we here conclude that this new method for the construction of size-fractionated cDNA libraries makes it possible to analyze cDNAs efficiently and comprehensively.

Animals↗