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  • 1
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    Online Resource
    Shigella IpaH7.8 E3 ubiquitin ligase targets glomulin and activates inflammasomes to demolish macrophages
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 40 ( 2014-10-07)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 40 ( 2014-10-07)
    Abstract: When nucleotide-binding oligomerization domain–like receptors (NLRs) sense cytosolic-invading bacteria, they induce the formation of inflammasomes and initiate an innate immune response. In quiescent cells, inflammasome activity is tightly regulated to prevent excess inflammation and cell death. Many bacterial pathogens provoke inflammasome activity and induce inflammatory responses, including cell death, by delivering type III secreted effectors, the rod component flagellin, and toxins. Recent studies indicated that Shigella deploy multiple mechanisms to stimulate NLR inflammasomes through type III secretion during infection. Here, we show that Shigella induces rapid macrophage cell death by delivering the invasion plasmid antigen H7.8 (IpaH7.8) enzyme 3 (E3) ubiquitin ligase effector via the type III secretion system, thereby activating the NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasomes and caspase-1 and leading to macrophage cell death in an IpaH7.8 E3 ligase-dependent manner. Mice infected with Shigella possessing IpaH7.8, but not with Shigella possessing an IpaH7.8 E3 ligase-null mutant, exhibited enhanced bacterial multiplication. We defined glomulin/flagellar-associated protein 68 (GLMN) as an IpaH7.8 target involved in IpaH7.8 E3 ligase-dependent inflammasome activation. This protein originally was identified through its association with glomuvenous malformations and more recently was described as a member of a Cullin ring ligase inhibitor. Modifying GLMN levels through overexpression or knockdown led to reduced or augmented inflammasome activation, respectively. Macrophages stimulated with lipopolysaccharide/ATP induced GLMN puncta that localized with the active form of caspase-1. Macrophages from GLMN +/− mice were more responsive to inflammasome activation than those from GLMN +/+ mice. Together, these results highlight a unique bacterial adaptation that hijacks inflammasome activation via interactions between IpaH7.8 and GLMN.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1324021111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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    SSG: 11
    SSG: 12
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  • 2
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    Radiation dose rates now and in the future for residents neighboring restricted areas of the Fukushima Daiichi Nuclear Power Plant
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 10 ( 2014-03-11)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 10 ( 2014-03-11)
    Abstract: Radiation dose rates were evaluated in three areas neighboring a restricted area within a 20- to 50-km radius of the Fukushima Daiichi Nuclear Power Plant in August–September 2012 and projected to 2022 and 2062. Study participants wore personal dosimeters measuring external dose equivalents, almost entirely from deposited radionuclides (groundshine). External dose rate equivalents owing to the accident averaged 1.03, 2.75, and 1.66 mSv/y in the village of Kawauchi, the Tamano area of Soma, and the Haramachi area of Minamisoma, respectively. Internal dose rates estimated from dietary intake of radiocesium averaged 0.0058, 0.019, and 0.0088 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. Dose rates from inhalation of resuspended radiocesium were lower than 0.001 mSv/y. In 2012, the average annual doses from radiocesium were close to the average background radiation exposure (2 mSv/y) in Japan. Accounting only for the physical decay of radiocesium, mean annual dose rates in 2022 were estimated as 0.31, 0.87, and 0.53 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. The simple and conservative estimates are comparable with variations in the background dose, and unlikely to exceed the ordinary permissible dose rate (1 mSv/y) for the majority of the Fukushima population. Health risk assessment indicates that post-2012 doses will increase lifetime solid cancer, leukemia, and breast cancer incidences by 1.06%, 0.03% and 0.28% respectively, in Tamano. This assessment was derived from short-term observation with uncertainties and did not evaluate the first-year dose and radioiodine exposure. Nevertheless, this estimate provides perspective on the long-term radiation exposure levels in the three regions.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1315684111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
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    Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 14 ( 2014-04-08), p. 5289-5294
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 14 ( 2014-04-08), p. 5289-5294
    Abstract: Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1312717110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
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    Sexually dimorphic expression of Mafb regulates masculinization of the embryonic urethral formation
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 46 ( 2014-11-18), p. 16407-16412
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 46 ( 2014-11-18), p. 16407-16412
    Abstract: Masculinization of external genitalia is an essential process in the formation of the male reproductive system. Prominent characteristics of this masculinization are the organ size and the sexual differentiation of the urethra. Although androgen is a pivotal inducer of the masculinization, the regulatory mechanism under the control of androgen is still unknown. Here, we address this longstanding question about how androgen induces masculinization of the embryonic external genitalia through the identification of the v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (Mafb) gene. Mafb is expressed prominently in the mesenchyme of male genital tubercle (GT), the anlage of external genitalia. MAFB expression is rarely detected in the mesenchyme of female GTs. However, exposure to exogenous androgen induces its mesenchymal expression in female GTs. Furthermore, MAFB expression is prominently down-regulated in male GTs of androgen receptor ( Ar ) KO mice, indicating that AR signaling is necessary for its expression. It is revealed that Mafb KO male GTs exhibit defective embryonic urethral formation, giving insight into the common human congenital anomaly hypospadias. However, the size of Mafb KO male GTs is similar with that of wild-type males. Moreover, androgen treatment fails to induce urethral masculinization of the GTs in Mafb KO mice. The current results provide evidence that Mafb is an androgen-inducible, sexually dimorphic regulator of embryonic urethral masculinization.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1413273111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 5
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    An exploratory study for analyzing interactional processes of group discussion: the case of a focus group interview
    Springer Science and Business Media LLC ; 2009
    In:  AI & SOCIETY Vol. 23, No. 2 ( 2009-3), p. 233-249
    Details
    In: AI & SOCIETY, Springer Science and Business Media LLC, Vol. 23, No. 2 ( 2009-3), p. 233-249
    Type of Medium: Online Resource
    ISSN: 0951-5666 , 1435-5655
    URL: Article
    DOI: 10.1007/s00146-007-0176-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
    detail.hit.zdb_id: 1458413-X
    detail.hit.zdb_id: 383872-9
    SSG: 7,11
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  • 6
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    Negative Feedback Regulation Ensures the One Receptor-One Olfactory Neuron Rule in Mouse
    American Association for the Advancement of Science (AAAS) ; 2003
    In:  Science Vol. 302, No. 5653 ( 2003-12-19), p. 2088-2094
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 302, No. 5653 ( 2003-12-19), p. 2088-2094
    Abstract: In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses only one odorant receptor (OR) gene in a monoallelic and mutually exclusive manner. Such expression forms the genetic basis for OR-instructed axonal projection of OSNs to the olfactory bulb of the brain during development. Here, we identify an upstream cis-acting DNA region that activates the OR gene cluster in mouse and allows the expression of only one OR gene within the cluster. Deletion of the coding region of the expressed OR gene or a naturally occurring frame-shift mutation allows a second OR gene to be expressed. We propose that stochastic activation of only one OR gene within the cluster and negative feedback regulation by that OR gene product are necessary to ensure the one receptor–one neuron rule.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1089122
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2003
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 7
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    Comparative Effects of Auditory Electromyographic Biofeedback for Participants Who Are Blind and Sighted
    SAGE Publications ; 2018
    In:  Perceptual and Motor Skills Vol. 125, No. 4 ( 2018-08), p. 732-748
    Details
    In: Perceptual and Motor Skills, SAGE Publications, Vol. 125, No. 4 ( 2018-08), p. 732-748
    Abstract: This study examined differences in auditory electromyographic biofeedback (AEB) effects between participants who were sighted and blind. Past research makes clear that AEB is effective for people who are blind, particularly because of their reported superiority in auditory processing, but no study has directly compared AEB efficacy between participants who are sighted and blind. A total of 11 participants who were sighted and 10 who were blind performed a motor task requiring 20 nonfatiguing muscle contractions at 20% maximal voluntary contraction (MVC) with or without AEB. AEB reduced the error (calculated as the absolute difference of two consecutive contractions) among both participant groups, and the error for the group without biofeedback was greater for the participants who were blind than that for the sighted participants (5.20% ± 2.05% MVC and 3.30% ± 1.26% MVC, respectively; p  〈  .05). This finding was consistent with subjective rating data, also indicating a trend toward greater difficulty for participants who were blind when performing without biofeedback. Moreover, the AEB/no biofeedback condition showed fewer errors for the participants who were blind than for the participants who were sighted during the last part of the task ( p = .036), indicating that participants who were blind were better at maintaining the AEB effect. These data suggest that the poor motor performance of participants who were blind was greatly improved with AEB, suggesting important applications of AEB for assistive technologies, adapted sports, and activities of daily living.
    Type of Medium: Online Resource
    ISSN: 0031-5125 , 1558-688X
    URL: Article
    DOI: 10.1177/0031512518777597
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2066876-4
    SSG: 5,2
    SSG: 7,11
    SSG: 31
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  • 8
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    A Myelin Galactolipid, Sulfatide, Is Essential for Maintenance of Ion Channels on Myelinated Axon But Not Essential for Initial Cluster Formation
    Society for Neuroscience ; 2002
    In:  The Journal of Neuroscience Vol. 22, No. 15 ( 2002-08-01), p. 6507-6514
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 22, No. 15 ( 2002-08-01), p. 6507-6514
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.22-15-06507.2002
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2002
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 9
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    Coexpression of Microsomal-Type Prostaglandin E Synthase with Cyclooxygenase-2 in Brain Endothelial Cells of Rats during Endotoxin-Induced Fever
    Society for Neuroscience ; 2001
    In:  The Journal of Neuroscience Vol. 21, No. 8 ( 2001-04-15), p. 2669-2677
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 21, No. 8 ( 2001-04-15), p. 2669-2677
    Abstract: Fever is triggered by an elevation of prostaglandin E 2 (PGE 2 ) in the brain. However, the mechanism of its elevation remains unanswered. We herein cloned the rat glutathione-dependent microsomal prostaglandin E synthase (mPGES), the terminal enzyme for PGE 2 biosynthesis, and examined its induction in the rat brain after intraperitoneal injection of pyrogen lipopolysaccharide (LPS). In Northern blot analysis, mPGES mRNA was weakly expressed in the brain under the normal conditions but was markedly induced between 2 and 4 hr after the LPS injection. In situ hybridization study revealed that LPS-induced mPGES mRNA signals were mainly associated with brain blood vessels, especially vein or venular-type ones, in the whole brain area. Immunohistochemical study demonstrated that mPGES-like immunoreactivity was expressed in the perinuclear region of brain endothelial cells, which were identified as von Willebrand factor-positive cells. Furthermore, in the perinuclear region of the endothelial cells, mPGES was colocalized with cyclooxygenase-2 (COX-2), which is the enzyme essential for the production of the mPGES substrate PGH 2 . Inhibition of cyclooxygenase-2 activity resulted in suppression of both PGE 2 level in the CSF and fever (Cao et al., 1997), suggesting that the two enzymes were functionally linked and that this link is essential for fever. These results demonstrate that brain endothelial cells play an essential role in the PGE 2 production during fever by expressing COX-2 and mPGES.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.21-08-02669.2001
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2001
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 10
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    Prime Minister Abe’s challenge to the Japanese Postwar Constitution
    John Benjamins Publishing Company ; 2018
    In:  Journal of Argumentation in Context Vol. 7, No. 1 ( 2018-5-7), p. 18-32
    Details
    In: Journal of Argumentation in Context, John Benjamins Publishing Company, Vol. 7, No. 1 ( 2018-5-7), p. 18-32
    Abstract: Japan has transformed itself from a militaristic, imperialist state into a pacifist, democratic country as well as a reliable U.S. ally. However, postwar Japan has had two responses to the lost war. On the one hand, conservatives often found it difficult to reconcile themselves with the reality of losing the last war. On the other hand, liberals found themselves at home in line with the Japanese postwar democracy based on the country’s embrace of the no war ideal. Taking into account the tension intrinsic to Japanese interpretations of the postwar Constitution, this study will explore the way in which Prime Minister Abe made confrontational strategic maneuvering in political argumentation. By doing so, it will explicate how Abe sought to identify the context in the way that one should view a reality.
    Type of Medium: Online Resource
    ISSN: 2211-4742 , 2211-4750
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.1075/jaic.7.1
    DOI: 10.1075/jaic
    DOI: 10.1075/jaic.16008.oku
    Language: English
    Publisher: John Benjamins Publishing Company
    Publication Date: 2018
    SSG: 7,11
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