Transcriptional Regulation of ATP2C1 Gene by Sp1 and YY1 and Reduced Function of its Promoter in Hailey–Hailey Disease Keratinocytes

Hailey–Hailey disease (HHD) is a blistering skin disease caused by malfunction of the Ca2+-dependent ATPase, ATP2C1. In this study, key regulatory regions necessary for the expression of the gene encoding human ATP2C1 were investigated. The transient reporter assay demonstrated that region +21/+57 was necessary for activation of the ATP2C1 promoter, and the electrophoretic mobility shift assay demonstrated that the region was recognized by the transcription factors, Sp1 and YY1. In accordance with this result, when Sp1 or YY1 was overexpressed in keratinocytes, an obvious increase in ATP2C1 promoter activity was observed, which was in contrast with the case where a mutant promoter lacking the binding sites for Sp1 and YY1 was used as the reporter. Ca2+-stimulation signal increased nuclear Sp1 proteins and ATP2C1 mRNA levels in normal keratinocytes. In contrast, both these increases were suppressed in keratinocytes from HHD patients. These results indicate that Sp1 and YY1 transactivate the human ATP2C1 promoter via cis-enhancing elements and that incomplete upregulation of ATP2C1 transcription contributes to the keratinocyte-specific pathogenesis of HHD. This is a report describing the regulation of the expression of ATP2C1

Graft rejection and hyperacute graft-versus-host disease in stem cell transplantation from non-inherited maternal antigen complementary HLA-mismatched siblings

金沢大学大学院医学系研究科機能再生学Human leukocyte antigen (HLA)-mismatched stem cell transplantation from non-inherited maternal antigen (NIMA)-complementary donors is known to produce stable engraftment without inducing severe graft-versus-host disease (GVHD). We treated two patients with acute myeloid leukemia (AML) and one patient with severe aplastic anemia (SAA) with HLA-mismatched stem cell transplantation (SCT) from NIMA-complementary donors (NIMA-mismatched SCT). The presence of donor and recipient-derived blood cells in the peripheral blood of recipient (donor microchimerism) and donor was documented respectively by amplifying NIMA-derived DNA in two of the three patients. Graft rejection occurred in the SAA patient who was conditioned with a fludarabine-based regimen. Grade III and grade IV acute GVHD developed in patients with AML on day 8 and day 11 respectively, and became a direct cause of death in one patient. The findings suggest that intensive conditioning and immunosuppression after stem cell transplantation are needed in NIMA-mismatched SCT even if donor and recipient microchimerisms is detectable in the donor and recipient before SCT. © 2007 The Authors

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Haematozoa of the Great Blue Turacos, Corythaeola cristata (Vieillot, 1816) (Aves: Musophagiformes: Musophagidae) imported to Singapore Jurong Bird Park with description and molecular characterisation of Haemoproteus (Parahaemoproteus) minchini new species (Apicomplexa: Haemosporidia: Haemoproteidae)

Chavatte, Jean-Marc, Okumura, Chiharu, Landau, Irène (2017): Haematozoa of the Great Blue Turacos, Corythaeola cristata (Vieillot, 1816) (Aves: Musophagiformes: Musophagidae) imported to Singapore Jurong Bird Park with description and molecular characterisation of Haemoproteus (Parahaemoproteus) minchini new species (Apicomplexa: Haemosporidia: Haemoproteidae). Raffles Bulletin of Zoology 65: 325-340, DOI: http://doi.org/10.5281/zenodo.535660

シンガポール・ジュロン鳥類公園のアカハシコサイチョウ（Tockus erythrorhynchus）で確認されたCyclocoelidae科吸虫について

On January 2013, a female red-billed hornbill, Tockus erythrorhvnchus. kept in Jurong Bird Park, Singapore, was admitted with severe dyspnea with high pitch sound. It vomited reddish fluid and was recumbent. It stood up for a few minutes after oxygenation, but became unresponsive again and died shortly after. At necropsy, many trematodes were collected from the air-sacs, lungs and trachea. Based on their morphology, the trematodes were identified as Szidatitrema sp. (Cyclocoelidae). This is the first record of a cyclocoelid species from the red-billed hornbill. Taking the life cycle of the family Cyclocoelidae into consideration, the case might have swallowed a certain snail with the metacercaria of the trematode. There has been no report on the pathological effect to the host bird by the trematode, but the severe respiratory symptom found in the present case might be provoked by the trematode.　2013年1月、シンガポールのジュロン鳥類公園で飼育するアカハシコサイチョウ(Tockus erythrorhynchus)が著しい呼吸促迫ならびに赤色液状物吐出を主徴とした呼吸器症状を呈して斃死した。この個体の気嚢および肺・気管からCyclocoelidae科吸虫が発見された。Szidatitrema属と同定されたが、種同定は良好な標本の再採集の機会を待ちたい。本科吸虫の生活史の特色として、中間宿主となる貝内にメタセルカリア寄生も起こることが知られていることから、そのような貝類摂取による感染が推測される。この鳥種からCyclocoelidae科吸虫が発見されたのは初めてであった。少数寄生では宿主に与える影響は小さいと考えられるが、今回の症例は呼吸困難な状態で斃死し、剖検で呼吸器系に多数虫体が確認されていたことから、死因の一部となっていたことが考えられた

Numerical results for ordinary and partial differential equations describing motions of elastic materials

We discuss an ordinary differential equation system proposed in [1] as a mathematical model for shrinking and stretching motions of elastic materials. Also, a numerical scheme due to the structure-preserving numerical method was constructed. Our aim of this paper is to compare the numerical results for periodic solutions by several methods in order to investigate their accuracy. We note that a proof for existence of periodic solutions of the ODE system is given. Finally, we derive a partial differential equation model from the ODE system and show numerical results for the PDE model

PU.1 Suppresses Th2 Cytokine Expression via Silencing of GATA3 Transcription in Dendritic Cells.

The transcription factor PU.1 is predominantly expressed in dendritic cells (DCs) and is essential for DC differentiation. Although there are several reports that PU.1 positively regulates the expression of DC-specific genes, whether PU.1 also has a suppressive effect on DCs is largely unknown. Here we demonstrate that PU.1 suppresses the expression of Th2 cytokines including IL-13 and IL-5 in bone marrow-derived DCs (BMDCs), through repression of the expression of GATA3, which is a master regulator of Th2 differentiations. When PU.1 siRNA was introduced into BMDCs, LPS-induced expression of IL-13 and IL-5 was increased along with upregulation of the constitutive expression of GATA2 and GATA3. The additional introduction of GATA3 siRNA but not of GATA2 siRNA abrogated PU.1 siRNA-mediated upregulation of IL-13 and IL-5. A chromatin immunoprecipitation assay showed that PU.1 bound to Gata3 proximal promoter region, which is more dominant than the distal promoter in driving GATA3 transcription in DCs. The degree of histone acetylation at the Gata3 promoter was decreased in PU.1 siRNA-introduced DCs, suggesting the involvement of PU.1 in chromatin modification of the Gata3 promoter. Treatment with a histone deacetylase (HDAC) inhibitor, trichostatin A, increased the degree of histone H3 acetylation at the Gata3 promoter and induced the subsequent expression of GATA3. Experiments using HDAC inhibitors and siRNAs showed that HDAC3 suppressed GATA3 expression. The recruitment of HDAC3 to the Gata3 promoter was decreased by PU.1 knockdown. LPS-induced IL-13 expression was dramatically reduced in BMDCs generated from mice lacking the conserved GATA3 response element, termed CGRE, which is an essential site for the binding of GATA3 on the Il-13 promoter. The degree of H3K4me3 at CGRE was significantly increased in PU.1 siRNA-transfected stimulated DCs. Our results indicate that PU.1 plays pivotal roles in DC development and function, serving not only as a transcriptional activator but also as a repressor