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  • 1
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    Dominant mutations in ORAI1 cause tubular aggregate myopathy with hypocalcemia via constitutive activation of store-operated Ca2+ channels (2015)
    Oxford University Press
    Details
    Publication Date: 2015-01-13
    Description: The store-operated Ca 2+ release-activated Ca 2+ (CRAC) channel is activated by diminished luminal Ca 2+ levels in the endoplasmic reticulum and sarcoplasmic reticulum (SR), and constitutes one of the major Ca 2+ entry pathways in various tissues. Tubular aggregates (TAs) are abnormal structures in the skeletal muscle, and although their mechanism of formation has not been clarified, altered Ca 2+ homeostasis related to a disordered SR is suggested to be one of the main contributing factors. TA myopathy is a hereditary muscle disorder that is pathologically characterized by the presence of TAs. Recently, dominant mutations in the STIM1 gene, encoding a Ca 2+ sensor that controls CRAC channels, have been identified to cause tubular aggregate myopathy (TAM). Here, we identified heterozygous missense mutations in the ORAI1 gene, encoding the CRAC channel itself, in three families affected by dominantly inherited TAM with hypocalcemia. Skeletal myotubes from an affected individual and HEK293 cells expressing mutated ORAI1 proteins displayed spontaneous extracellular Ca 2+ entry into cells without diminishment of luminal Ca 2+ or the association with STIM1. Our results indicate that STIM1-independent activation of CRAC channels induced by dominant mutations in ORAI1 cause altered Ca 2+ homeostasis, resulting in TAM with hypocalcemia.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-24
    Description: Vacuolar H + -ATPase (V-ATPase) is responsible for the acidification of eukaryotic intracellular compartments and plays an important role in oxidative stress response (OSR), but its molecular bases are largely unknown. Here, we investigated how V-ATPase is involved in the OSR by using a strain lacking VPH2 , which encodes an assembly factor of V-ATPase, in the pathogenic fungus Candida glabrata . The loss of Vph2 resulted in increased H 2 O 2 sensitivity and intracellular reactive oxygen species (ROS) level independently of mitochondrial functions. The vph2 mutant also displayed growth defects under alkaline conditions accompanied by the accumulation of intracellular ROS and these phenotypes were recovered in the presence of the ROS scavenger N-acetyl- l -cysteine. Both expression and activity levels of mitochondrial manganese superoxide dismutase (Sod2) and catalase (Cta1) were decreased in the vph2 mutant. Phenotypic analyses of strains lacking and overexpressing these genes revealed that Sod2 and Cta1 play a predominant role in endogenous and exogenous OSR, respectively. Furthermore, supplementation of copper and iron restored the expression of SOD2 specifically in the vph2 mutant, suggesting that the homeostasis of intracellular cupper and iron levels maintained by V-ATPase was important for the Sod2-mediated OSR. This report demonstrates novel roles of V-ATPase in the OSR in C. glabrata .
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Modeling of Interfacial Dynamic Slip Pulses with Slip-Weakening Friction (2016)
    Seismological Society of America (SSA)
    Details
    Publication Date: 2016-07-26
    Description: Dynamic slip pulse propagation along a material interface is of great interest because many faults are known to lie along material interfaces and such interfaces may cause pulse-like ruptures. This subject has been extensively studied numerically over the last two decades. It has not, however, been studied very thoroughly from an analytical standpoint, although analytical studies would complement numerical ones. In particular, an analytical solution for removing stress singularities has not yet been obtained, even after an asymptotic analysis. In this article, we employ three physically plausible conditions in our theoretical modeling: (1) arbitrary propagation speeds in the sub-Rayleigh range, (2) a slip-weakening friction law, and (3) boundedness of stress. We can construct an analytical solution under these conditions, and as a result of our parameter study, we determine the dependence of slip-weakening distance and the ratio of process zone size to pulse length on rupture direction and velocity. These results enable us to discuss a mechanism for limiting rupture velocity and estimating the slip-weakening distance in seismic inversion analyses.
    Print ISSN: 0037-1106
    Electronic ISSN: 1943-3573
    Topics: Geosciences , Physics
    Published by Seismological Society of America (SSA)
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  • 4
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    Preparation and characterization of a monoclonal antibody against the refolded and functional extracellular domain of rat P2X4 receptor (2013)
    Oxford University Press
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    Publication Date: 2013-02-13
    Description: The P2X4 purinergic receptor is a key molecule in neuropathic pain, particularly in the allodynia after peripheral nerve injury. We therefore sought to establish an anti-P2X4 receptor monoclonal antibody that would be useful for detection and characterization of the P2X4 receptor. We first prepared the refolded extracellular domain of the rat P2X4 receptor expressed in Escherichia coli . Then, we established a B-cell hybridoma producing the monoclonal antibody for the head domain of the rat P2X4 receptor with strict recognition, including S-S bond formation. In addition, we succeeded in the detection and immune precipitation of rat P2X4 receptor molecules on cultured cells. As the antibody specifically binds to the rat P2X4 receptor molecule, it is expected that the established monoclonal antibody will be applicable as a tool for detecting increasing expression levels of the P2X4 receptor molecule accompanied with increasing intensity of neuropathic pain.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
    Published by Oxford University Press on behalf of The Japanese Biochemical Society (JBS).
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  • 5
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    Structure–Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the Treatment of Acute Severe Pain (2013)
    American Chemical Society (ACS)
    Details
    Publication Date: 2013-10-15
    Description: Journal of Medicinal Chemistry DOI: 10.1021/jm4010829
    Topics: Chemistry and Pharmacology
    Published by American Chemical Society (ACS)
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  • 6
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    Crystal orientation mechanism of ZnTe epilayers formed on different orientations of sapphire substrates by molecular beam epitaxy (2014)
    American Institute of Physics (AIP)
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    Publication Date: 2014-11-01
    Description: The electrooptic effect in ZnTe has recently attracted research attention, and various device structures using ZnTe have been explored. For application to practical terahertz wave detector devices based on ZnTe thin films, sapphire substrates are preferred because they enable the optical path alignment to be simplified. ZnTe/sapphire heterostructures were focused upon, and ZnTe epilayers were prepared on highly mismatched sapphire substrates by molecular beam epitaxy. Epitaxial relationships between the ZnTe thin films and the sapphire substrates with their various orientations were investigated using an X-ray diffraction pole figure method. (0001) c -plane, (1-102) r -plane, (1-100) m -plane, and (11-20) a -plane oriented sapphire substrates were used in this study. The epitaxial relationship between ZnTe and c -plane sapphire was found to be (111) ZnTe//(0001) sapphire with an in-plane orientation relationship of [−211] ZnTe//[1-100] sapphire. It was found that the (211)-plane ZnTe layer was grown on the m -plane of the sapphire substrates, and the (100)-plane ZnTe layer was grown on the r -plane sapphire. When the sapphire substrates were inclined from the c -plane towards the m -axis direction, the orientation of the ZnTe thin films was then tilted from the (111)-plane to the (211)-plane. The c -plane of the sapphire substrates governs the formation of the (111) ZnTe domain and the ZnTe epilayer orientation. These crystallographic features were also related to the atom arrangements of ZnTe and sapphire.
    Print ISSN: 0021-8979
    Electronic ISSN: 1089-7550
    Topics: Physics
    Published by American Institute of Physics (AIP)
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  • 7
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    Dynamic antiplane rupture propagation crossing a material interface: modelling with BIEM (2015)
    Oxford University Press
    Details
    Publication Date: 2015-01-08
    Description: Because the Earth's crust is quite heterogeneous and consists of various types of rocks, many faults are located near material interfaces. Recent observational studies have revealed that some faults cross the interfaces, but theoretical treatment of their dynamic behaviour is still undeveloped. In this paper, we develop a boundary integral equation method (BIEM) to analyse the dynamic behaviour of antiplane rupture propagation crossing a material interface. First, we obtain an exact solution of the stress response due to a rectangular slip rate function on one discretized crack element embedded in one of the elastic half-spaces welded along a planar interface. This solution is helpful not only in BIEM simulations of rupture propagation but also in benchmark testing or extension of other numerical schemes. Next, we simulate the dynamic propagation of an antiplane rupture crossing the material interface by using the exact solution for a stress response in a BIEM framework. We find that a shear wave reflected from the material interface generates a significant change in the slip rate on the crack depending on the angle between the interface and the crack, contrast in the elastic properties, and rupture velocity. Moreover, we infer from our numerical results and previous related works that a backward propagating healing front emerges under rate-weakening friction owing to interaction between the reflected wave and friction.
    Keywords: Seismology
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 8
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    Quantifying sequence and structural features of protein-RNA interactions (2014)
    Oxford University Press
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    Publication Date: 2014-09-02
    Description: Increasing awareness of the importance of protein–RNA interactions has motivated many approaches to predict residue-level RNA binding sites in proteins based on sequence or structural characteristics. Sequence-based predictors are usually high in sensitivity but low in specificity; conversely structure-based predictors tend to have high specificity, but lower sensitivity. Here we quantified the contribution of both sequence- and structure-based features as indicators of RNA-binding propensity using a machine-learning approach. In order to capture structural information for proteins without a known structure, we used homology modeling to extract the relevant structural features. Several novel and modified features enhanced the accuracy of residue-level RNA-binding propensity beyond what has been reported previously, including by meta-prediction servers. These features include: hidden Markov model-based evolutionary conservation, surface deformations based on the Laplacian norm formalism, and relative solvent accessibility partitioned into backbone and side chain contributions. We constructed a web server called aaRNA that implements the proposed method and demonstrate its use in identifying putative RNA binding sites.
    Keywords: Protein-nucleic acid interaction
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Retraction (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-10-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fukuhara, Atsunori -- Matsuda, Morihiro -- Nishizawa, Masako -- Segawa, Katsumori -- Tanaka, Masaki -- Kishimoto, Kae -- Matsuki, Yasushi -- Murakami, Mirei -- Ichisaka, Tomoko -- Murakami, Hiroko -- Watanabe, Eijiro -- Takagi, Toshiyuki -- Akiyoshi, Megumi -- Ohtsubo, Tsuguteru -- Kihara, Shinji -- Yamashita, Shizuya -- Makishima, Makoto -- Funahashi, Tohru -- Yamanaka, Shinya -- Hiramatsu, Ryuji -- Matsuzawa, Yuji -- Shimomura, Iichiro -- New York, N.Y. -- Science. 2007 Oct 26;318(5850):565.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17962537" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    Visfatin: a protein secreted by visceral fat that mimics the effects of insulin (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-12-18
    Description: Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fukuhara, Atsunori -- Matsuda, Morihiro -- Nishizawa, Masako -- Segawa, Katsumori -- Tanaka, Masaki -- Kishimoto, Kae -- Matsuki, Yasushi -- Murakami, Mirei -- Ichisaka, Tomoko -- Murakami, Hiroko -- Watanabe, Eijiro -- Takagi, Toshiyuki -- Akiyoshi, Megumi -- Ohtsubo, Tsuguteru -- Kihara, Shinji -- Yamashita, Shizuya -- Makishima, Makoto -- Funahashi, Tohru -- Yamanaka, Shinya -- Hiramatsu, Ryuji -- Matsuzawa, Yuji -- Shimomura, Iichiro -- New York, N.Y. -- Science. 2005 Jan 21;307(5708):426-30. Epub 2004 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Pathophysiology, Graduate School of Medicine, and Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15604363" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/drug effects/metabolism ; Adipose Tissue/*metabolism ; Animals ; Binding Sites ; Blood Glucose/analysis ; Cell Line ; Cells, Cultured ; Cytokines/blood/genetics/*metabolism/pharmacology ; Diabetes Mellitus, Type 2/metabolism ; Dose-Response Relationship, Drug ; Female ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Gene Targeting ; Humans ; Insulin/blood/*metabolism ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Molecular Mimicry ; Muscle Cells/metabolism ; Nicotinamide Phosphoribosyltransferase ; Phosphorylation ; Receptor, Insulin/metabolism ; Recombinant Proteins/pharmacology ; Signal Transduction ; Subcutaneous Tissue ; Viscera
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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