Hiroshima University

About: Hiroshima University is a education organization based out in Hiroshima, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 33602 authors who have published 69290 publications receiving 1495648 citations. The organization is also known as: Hiroshima Daigaku.

Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia

Abstract: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies. Our previous hematological analysis indicated similarities between human CAMT and murine c-mpl (thrombopoietin receptor) deficiency. Because the c-mpl gene was considered as one of the candidate genes for this disorder, we analyzed the genomic sequence of the c-mpl gene of a 10-year-old Japanese girl with CAMT. We detected two heterozygous point mutations: a C-to-T transition at the cDNA nucleotide position 556 (Q186X) in exon 4 and a single nucleotide deletion of thymine at position 1,499 (1,499 delT) in exon 10. Both mutations were predicted to result in a prematurely terminated c-Mpl protein, which, if translated, lacks all intracellular domains essential for signal transduction. Each of the mutations was segregated from the patient’s parents. Accordingly, the patient was a compound heterozygote for two mutations of the c-mpl gene, each derived from one of the parents. The present study suggests that at least a certain type of CAMT is caused by the c-mpl mutation, which disrupts the function of thrombopoietin receptor.

Synthesis and Spectroscopic Properties of a Series of β-Blocked Long Oligothiophenes up to the 96-mer: Revaluation of Effective Conjugation Length

Abstract: A series of extraordinarily long oligothiophenes up to the 96-mer has been developed by iterative oxidative coupling of the completely beta-blocked sexithiophene. They are highly conjugated like nonsubstituted oligothiophenes, and the effective conjugation of this system is extended to 96 thiophene units and much longer than that previously speculated for polythiophenes.

FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway.

Abstract: In response to DNA damage or replication fork stress, the Fanconi anemia pathway is activated, leading to monoubiquitination of FANCD2 and FANCI and their colocalization in foci. Here we show that, in the chicken DT40 cell system, multiple alanine-substitution mutations in six conserved and clustered Ser/Thr-Gln motifs of FANCI largely abrogate monoubiquitination and focus formation of both FANCI and FANCD2, resulting in loss of DNA repair function. Conversely, FANCI carrying phosphomimic mutations on the same six residues induces constitutive monoubiquitination and focus formation of FANCI and FANCD2, and protects against cell killing and chromosome breakage by DNA interstrand cross-linking agents. We propose that the multiple phosphorylation of FANCI serves as a molecular switch in activation of the Fanconi anemia pathway. Mutational analysis of putative phosphorylation sites in human FANCI indicates that this switch is evolutionarily conserved.

Origin of the metallic properties of heavily boron-doped superconducting diamond

Abstract: The recent discovery that heavily boron-doped diamond is a superconductor with a transition temperature of 7.4 K raises the prospect of superconducting devices with the unique properties of diamond. A study of the electronic structure responsible for superconductivity in heavily boron-doped diamond supports the idea that superconductivity is phonon-mediated, and provides information on the electronic structure that must be retained in order to harness this effect in practical devices. The physical properties of lightly doped semiconductors are well described by electronic band-structure calculations and impurity energy levels1. Such properties form the basis of present-day semiconductor technology. If the doping concentration n exceeds a critical value nc, the system passes through an insulator-to-metal transition and exhibits metallic behaviour; this is widely accepted to occur as a consequence of the impurity levels merging to form energy bands2. However, the electronic structure of semiconductors doped beyond nc have not been explored in detail. Therefore, the recent observation of superconductivity emerging near the insulator-to-metal transition3 in heavily boron-doped diamond4,5 has stimulated a discussion on the fundamental origin of the metallic states responsible for the superconductivity. Two approaches have been adopted for describing this metallic state: the introduction of charge carriers into either the impurity bands6 or the intrinsic diamond bands7,8,9. Here we show experimentally that the doping-dependent occupied electronic structures are consistent with the diamond bands, indicating that holes in the diamond bands play an essential part in determining the metallic nature of the heavily boron-doped diamond superconductor. This supports the diamond band approach and related predictions, including the possibility of achieving dopant-induced superconductivity in silicon and germanium7. It should also provide a foundation for the possible development of diamond-based devices10.