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  1. Article ; Online: Nonthermal acceleration of protein hydration by sub-terahertz irradiation

    Jun-ichi Sugiyama / Yuji Tokunaga / Mafumi Hishida / Masahito Tanaka / Koh Takeuchi / Daisuke Satoh / Masahiko Imashimizu

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 13

    Abstract: Abstract The collective intermolecular dynamics of protein and water molecules, which overlap in the sub-terahertz (THz) frequency region, are relevant for expressing protein functions but remain largely unknown. This study used dielectric relaxation (DR) ...

    Abstract Abstract The collective intermolecular dynamics of protein and water molecules, which overlap in the sub-terahertz (THz) frequency region, are relevant for expressing protein functions but remain largely unknown. This study used dielectric relaxation (DR) measurements to investigate how externally applied sub-THz electromagnetic fields perturb the rapid collective dynamics and influence the considerably slower chemical processes in protein–water systems. We analyzed an aqueous lysozyme solution, whose hydration is not thermally equilibrated. By detecting time-lapse differences in microwave DR, we demonstrated that sub-THz irradiation gradually decreases the dielectric permittivity of the lysozyme solution by reducing the orientational polarization of water molecules. Comprehensive analysis combining THz and nuclear magnetic resonance spectroscopies suggested that the gradual decrease in the dielectric permittivity is not induced by heating but is due to a slow shift toward the hydrophobic hydration structure in lysozyme. Our findings can be used to investigate hydration-mediated protein functions based on sub-THz irradiation.
    Keywords Science ; Q
    Subject code 541
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Interactive Toxicogenomics

    Johan Nyström-Persson / Yayoi Natsume-Kitatani / Yoshinobu Igarashi / Daisuke Satoh / Kenji Mizuguchi

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    Gene set discovery, clustering and analysis in Toxygates

    2017  Volume 10

    Abstract: Abstract Toxygates was originally released as a user-friendly interface to enhance the accessibility of the large-scale toxicogenomics database, Open TG-GATEs, generated by the Japanese Toxicogenomics Project. Since the original release, significant new ... ...

    Abstract Abstract Toxygates was originally released as a user-friendly interface to enhance the accessibility of the large-scale toxicogenomics database, Open TG-GATEs, generated by the Japanese Toxicogenomics Project. Since the original release, significant new functionality has been added to enable users to perform sophisticated computational analysis with only modest bioinformatics skills. The new features include an orthologous mode for data comparison among different species, interactive clustering and heatmap visualisation, enrichment analysis of gene sets, and user data uploading. In a case study, we use these new functions to study the hepatotoxicity of peroxisome proliferator-activated receptor alpha (PPARα) agonist WY-14643. Our findings suggest that WY-14643 caused hypertrophy in the bile duct by intracellular Ca2+ dysregulation, which resulted in the induction of genes in a non-canonical WNT/Ca2+ signalling pathway. With this new release of Toxygates, we provide a suite of tools that allow anyone to carry out in-depth analysis of toxicogenomics in Open TG-GATEs, and of any other dataset that is uploaded.
    Keywords Medicine ; R ; Science ; Q
    Subject code 004
    Language English
    Publishing date 2017-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Establishment of a novel hepatocyte model that expresses four cytochrome P450 genes stably via mammalian-derived artificial chromosome for pharmacokinetics and toxicity studies.

    Daisuke Satoh / Satoru Iwado / Satoshi Abe / Kanako Kazuki / Shinobu Wakuri / Mitsuo Oshimura / Yasuhiro Kazuki

    PLoS ONE, Vol 12, Iss 10, p e

    2017  Volume 0187072

    Abstract: The utility of HepG2 cells to assess drug metabolism and toxicity induced by chemical compounds is hampered by their low cytochrome P450 (CYP) activities. To overcome this limitation, we established HepG2 cell lines expressing major CYP enzymes involved ... ...

    Abstract The utility of HepG2 cells to assess drug metabolism and toxicity induced by chemical compounds is hampered by their low cytochrome P450 (CYP) activities. To overcome this limitation, we established HepG2 cell lines expressing major CYP enzymes involved in drug metabolism (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and CYP oxidoreductase (POR) using the mammalian-derived artificial chromosome vector. Transchromosomic HepG2 (TC-HepG2) cells expressing four CYPs and POR were used to determine time- and concentration-dependent inhibition and toxicity of several compounds by luminescence detection of CYP-specific substrates and cell viability assays. Gene expression levels of all four CYPs and POR, as well as the CYP activities, were higher in TC-HepG2 clones than in parental HepG2 cells. Additionally, the activity levels of all CYPs were reduced in a concentration-dependent manner by specific CYP inhibitors. Furthermore, preincubation of TC-HepG2 cells with CYP inhibitors known as time-dependent inhibitors (TDI) prior to the addition of CYP-specific substrates determined that CYP inhibition was enhanced in the TDI group than in the non-TDI group. Finally, the IC50 of bioactivable compound aflatoxin B1 was lower in TC-HepG2 cells than in HepG2 cells. In conclusion, the TC-HepG2 cells characterized in the current study are a highly versatile model to evaluate drug-drug interactions and hepatotoxicity in initial screening of candidate drug compounds, which require a high degree of processing capacity and reliability.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets

    Upasana Maheshwari / Dominik Kraus / Nathalie Vilain / Sjoerd J.B. Holwerda / Vanja Cankovic / Nicola A. Maiorano / Hubertus Kohler / Daisuke Satoh / Markus Sigrist / Silvia Arber / Claudius F. Kratochwil / Thomas Di Meglio / Sebastien Ducret / Filippo M. Rijli

    Cell Reports, Vol 31, Iss 11, Pp 107767- (2020)

    2020  

    Abstract: Summary: The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are ... ...

    Abstract Summary: The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are largely unknown. We show that expression of Hox5 transcription factors is induced in specific subsets of postmitotic PN neurons at migration onset. Hox5 induction is achieved by response to retinoic acid signaling, resulting in Jmjd3-dependent derepression of Polycomb chromatin and 3D conformational changes. Hoxa5 drives neurons to settle posteriorly in the PN, where they are monosynaptically targeted by cortical neuron subsets mainly carrying limb somatosensation. Furthermore, Hoxa5 postmigratory ectopic expression in PN neurons is sufficient to attract cortical somatosensory inputs regardless of position and avoid visual afferents. Transcriptome analysis further suggests that Hoxa5 is involved in circuit formation. Thus, Hoxa5 coordinates postmitotic specification, migration, settling position, and sub-circuit assembly of PN neuron subsets in the cortico-cerebellar pathway.
    Keywords Hox transcription factor ; corticopontine circuit development ; precerebellar neurons ; retinoic acid ; neuronal positional identity ; somatosensory topographic connectivity map ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model

    Ryuta Imaki / Shinichi Niwano / Hiroe Niwano / Daisuke Satoh / Toru Yoshida / Yoshihiko Masaki / Tohru Izumi

    Indian Pacing and Electrophysiology Journal, Vol 8, Iss 2, Pp 102-

    2008  Volume 113

    Abstract: Introduction We examined the acute effects of neutral endopeptidase inhibitor on the hemodynamics and electrical properties of dogs subjected to rapid atrial pacing. Methods Ten beagle dogs were used and divided into two groups with and without ... ...

    Abstract Introduction We examined the acute effects of neutral endopeptidase inhibitor on the hemodynamics and electrical properties of dogs subjected to rapid atrial pacing. Methods Ten beagle dogs were used and divided into two groups with and without candoxatril, a neutral endopeptidase inhibitor preadministration. Before and after the 6 hours rapid atrial pacing from the right atrial appendage, the hemodynamics, atrial effective refractory period, and monophasic action potential duration of the right atrial appendage were measured and blood samples were collected. Atrial tissue was also excised after the experiment. Results Candoxatril significantly increased plasma ANP levels (Control: 88.4 ± 50.25 vs. Candoxatril: 197.1 ± 32.09 pg/ml, p = 0.004) and prevented reductions in atrial effective refractory period and monophasic action potential duration. We further demonstrated that the treated animals exhibited significantly higher levels of atrial tissue cyclic GMP (Control: 28.1 ± 1.60 fmol/mg vs. Candoxatril: 44.5 ± 12.28 fmol/mg, p = 0.034) as well as that of plasma cyclic GMP (Control: 32 ± 5.5 vs. Candoxatril: 42 ± 7.1 pg/ml, p = 0.028). Conclusion Candoxatril suppressed the shortening of atrial effective refractory period and monophasic action potential duration in the rapid atrial pacing model. As plasma ANP and the atrial tissue levels of cyclic GMP were higher in the Candoxatril group than the control, this effect was considered to appear through the reduction of calcium overload caused by ANP and cyclic GMP.
    Keywords electrical remodeling ; atrial natriuretic peptide ; neutral endopeptidase inhibitor ; cyclic GMP ; calcium ; Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Cardiovascular ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Physiology ; QP1-981 ; Science ; Q ; DOAJ:Physiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
    Subject code 630
    Language English
    Publishing date 2008-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: An essential role of the universal polarity protein, aPKClambda, on the maintenance of podocyte slit diaphragms.

    Tomonori Hirose / Daisuke Satoh / Hidetake Kurihara / Chiho Kusaka / Hiroko Hirose / Kazunori Akimoto / Taiji Matsusaka / Iekuni Ichikawa / Tetsuo Noda / Shigeo Ohno

    PLoS ONE, Vol 4, Iss 1, p e

    2009  Volume 4194

    Abstract: Glomerular visceral epithelial cells (podocytes) contain interdigitated processes that form specialized intercellular junctions, termed slit diaphragms, which provide a selective filtration barrier in the renal glomerulus. Analyses of disease-causing ... ...

    Abstract Glomerular visceral epithelial cells (podocytes) contain interdigitated processes that form specialized intercellular junctions, termed slit diaphragms, which provide a selective filtration barrier in the renal glomerulus. Analyses of disease-causing mutations in familial nephrotic syndromes and targeted mutagenesis in mice have revealed critical roles of several proteins in the assembly of slit diaphragms. The nephrin-podocin complex is the main constituent of slit diaphragms. However, the molecular mechanisms regulating these proteins to maintain the slit diaphragms are still largely unknown. Here, we demonstrate that the PAR3-atypical protein kinase C (aPKC)-PAR6beta cell polarity proteins co-localize to the slit diaphragms with nephrin. Furthermore, selective depletion of aPKClambda in mouse podocytes results in the disassembly of slit diaphragms, a disturbance in apico-basal cell polarity, and focal segmental glomerulosclerosis (FSGS). The aPKC-PAR3 complex associates with the nephrin-podocin complex in podocytes through direct interaction between PAR3 and nephrin, and the kinase activity of aPKC is required for the appropriate distribution of nephrin and podocin in podocytes. These observations not only establish a critical function of the polarity proteins in the maintenance of slit diaphragms, but also imply their potential involvement in renal failure in FSGS.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2009-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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