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Institution

Tokyo University of Science

EducationTokyo, Japan
About: Tokyo University of Science is a education organization based out in Tokyo, Japan. It is known for research contribution in the topics: Thin film & Enantioselective synthesis. The organization has 15800 authors who have published 24147 publications receiving 438081 citations. The organization is also known as: Tōkyō Rika Daigaku & Science University of Tokyo.


Papers
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Journal ArticleDOI
TL;DR: It is shown that deficiency of IL-1RI in cmo mice resulted in a significant reduction in the time to onset of disease as well as the degree of bone pathology, and an inflammasome-independent role forIL-1β in disease progression of cmo and implicate neutrophils and neutrophil serine proteases in disease pathogenesis.
Abstract: Chronic recurrent multifocal osteomyelitis (CRMO) is a human autoinflammatory disorder that primarily affects bone. Missense mutation (L98P) of proline-serine-threonine phosphatase-interacting protein 2 (Pstpip2) in mice leads to a disease that is phenotypically similar to CRMO called chronic multifocal osteomyelitis (cmo). Here we show that deficiency of IL-1RI in cmo mice resulted in a significant reduction in the time to onset of disease as well as the degree of bone pathology. Additionally, the proinflammatory cytokine IL-1β, but not IL-1α, played a critical role in the pathology observed in cmo mice. In contrast, disease in cmo mice was found to be independent of the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome as well as caspase-1. Neutrophils, but not bone marrow-derived macrophages, from cmo mice secreted increased IL-1β in response to ATP, silica, and Pseudomonas aeruginosa compared with neutrophils from WT mice. This aberrant neutrophil response was sensitive to inhibition by serine protease inhibitors. These results demonstrate an inflammasome-independent role for IL-1β in disease progression of cmo and implicate neutrophils and neutrophil serine proteases in disease pathogenesis. These data provide a rationale for directly targeting IL-1RI or IL-1β as a therapeutic strategy in CRMO.

113 citations

Journal ArticleDOI
TL;DR: In this paper, the magnetic field dependence of the characteristic energy relaxation time and echo phase relaxation time near the optimal operating point of a superconducting flux qubit was measured by means of the phase cycling method.
Abstract: In order to gain a better understanding of the origin of decoherence in superconducting flux qubits, we have measured the magnetic field dependence of the characteristic energy relaxation time (${T}_{1}$) and echo phase relaxation time (${T}_{2}^{\mathrm{echo}}$) near the optimal operating point of a flux qubit. We have measured ${T}_{2}^{\mathrm{echo}}$ by means of the phase cycling method. At the optimal point, we found the relation ${T}_{2}^{\mathrm{echo}}\ensuremath{\approx}2{T}_{1}$. This means that the echo decay time is limited by the energy relaxation (${T}_{1}$ process). Moving away from the optimal point, we observe a linear increase of the phase relaxation rate ($1/{T}_{2}^{\mathrm{echo}}$) with the applied external magnetic flux. This behavior can be well explained by the influence of magnetic flux noise with a $1/f$ spectrum on the qubit.

113 citations

Journal ArticleDOI
TL;DR: A comprehensive analysis of post-transcriptional modifications of all human mt-tRNAs, including 14 previously-uncharacterized species, provides insight into the molecular mechanisms underlying the decoding system and could help to elucidate the molecular pathogenesis of human mitochondrial diseases caused by aberrant tRNA modifications.
Abstract: Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. They are required for deciphering genetic code accurately, as well as stabilizing tRNA. Loss of tRNA modifications frequently results in severe pathological consequences. Here, we perform a comprehensive analysis of post-transcriptional modifications of all human mt-tRNAs, including 14 previously-uncharacterized species. In total, we find 18 kinds of RNA modifications at 137 positions (8.7% in 1575 nucleobases) in 22 species of human mt-tRNAs. An up-to-date list of 34 genes responsible for mt-tRNA modifications are provided. We identify two genes required for queuosine (Q) formation in mt-tRNAs. Our results provide insight into the molecular mechanisms underlying the decoding system and could help to elucidate the molecular pathogenesis of human mitochondrial diseases caused by aberrant tRNA modifications. Mitochondrial tRNA modifications are important for tRNA stability and accurate decoding. By employing RNA mass spectrometry and deep sequencing, here the authors provide a comprehensive analysis of post-transcriptional modifications of 22 species of human mitochondrial tRNAs.

113 citations

Journal ArticleDOI
13 Jan 2013-Nature
TL;DR: These asymmetric structures represent the first high-resolution view of the rotational mechanism of V1-ATPase from the A3B3 and DF complexes and suggest a binding order in the right-handed rotational orientation in a cooperative manner.
Abstract: Several crystal structures of the rotary motor of bacterial V-ATPase are solved at high resolution, representing different asymmetric structures and enabling the prediction of a model for the rotational mechanism of V1-ATPase. Vacuolar-type H+-ATPases (V-ATPases) are biomolecular rotary motors that couple ATP hydrolysis to the transport of a proton across intracellular and plasma membranes of eukaryotic cells. V-ATPase functions in many cellular processes and is an important drug target for diseases such as osteoporosis and cancer. This paper reports several X-ray crystal structures of a V1-ATPase from Enterococcus hirae, which reveal the conformational changes that occur when ATP binds the protein. On the basis of these structures the authors propose a model for the rotation mechanism of this membrane protein. In various cellular membrane systems, vacuolar ATPases (V-ATPases) function as proton pumps, which are involved in many processes such as bone resorption and cancer metastasis, and these membrane proteins represent attractive drug targets for osteoporosis and cancer1. The hydrophilic V1 portion is known as a rotary motor, in which a central axis DF complex rotates inside a hexagonally arranged catalytic A3B3 complex using ATP hydrolysis energy, but the molecular mechanism is not well defined owing to a lack of high-resolution structural information. We previously reported on the in vitro expression, purification and reconstitution of Enterococcus hirae V1-ATPase from the A3B3 and DF complexes2,3. Here we report the asymmetric structures of the nucleotide-free (2.8 A) and nucleotide-bound (3.4 A) A3B3 complex that demonstrate conformational changes induced by nucleotide binding, suggesting a binding order in the right-handed rotational orientation in a cooperative manner. The crystal structures of the nucleotide-free (2.2 A) and nucleotide-bound (2.7 A) V1-ATPase are also reported. The more tightly packed nucleotide-binding site seems to be induced by DF binding, and ATP hydrolysis seems to be stimulated by the approach of a conserved arginine residue. To our knowledge, these asymmetric structures represent the first high-resolution view of the rotational mechanism of V1-ATPase.

113 citations

Journal ArticleDOI
TL;DR: It is found that Il17f–/− mice resisted chemically induced colitis, but Il17a–/– mice did not, and that IL17f−/− CD45RBhiCD4+ T cells induced milder colitis in lymphocyte-deficient Rag2–/- mice, accompanied by an increase in intestinal regulatory T cells (Treg cells).
Abstract: The cytokines IL-17A and IL-17F have 50% amino-acid identity and bind the same receptor; however, their functional differences have remained obscure. Here we found that Il17f-/- mice resisted chemically induced colitis, but Il17a-/- mice did not, and that Il17f-/- CD45RBhiCD4+ T cells induced milder colitis in lymphocyte-deficient Rag2-/- mice, accompanied by an increase in intestinal regulatory T cells (Treg cells). Clostridium cluster XIVa in colonic microbiota capable of inducing Treg cells was increased in both Il17f-/- mice and mice given transfer Il17f-/- T cells, due to decreased expression of a group of antimicrobial proteins. There was substantial production of IL-17F, but not of IL-17A, not only by naive T cells but also by various colon-resident cells under physiological conditions. Furthermore, antibody to IL-17F suppressed the development of colitis, but antibody to IL-17A did not. These observations suggest that IL-17F is an effective target for the treatment of colitis.

113 citations


Authors

Showing all 15878 results

NameH-indexPapersCitations
Kazunori Kataoka13890870412
Yoichiro Iwakura12970564041
Kouji Matsushima12459056995
Masaki Ishitsuka10362439383
Shinsuke Tanabe9872237445
Tatsumi Koi9741150222
Hirofumi Akagi9461843179
Clifford A. Lowell9125823538
Teruo Okano9160528346
László Á. Gergely8942660674
T. Sumiyoshi8885562277
Toshinori Nakayama8640525275
Akihiko Kudo8632839475
Hans-Joachim Gabius8569928085
Motohide Tamura85100732725
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202356
2022137
20211,357
20201,481
20191,510
20181,429