Institution
Kyoto University
Education•Kyoto, Japan•
About: Kyoto University is a education organization based out in Kyoto, Japan. It is known for research contribution in the topics: Population & Catalysis. The organization has 85837 authors who have published 217215 publications receiving 6526826 citations. The organization is also known as: Kyōto University & Kyōto daigaku.
Topics: Population, Catalysis, Transplantation, Polymerization, Gene
Papers published on a yearly basis
Papers
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TL;DR: Results suggest that HES-1 normally controls the proper timing of neurogenesis and regulates neural tube morphogenesis.
Abstract: Mammalian hairy and Enhancer of split homolog-1 (HES-1) encodes a helix-loop-helix (HLH) factor that is thought to act as a negative regulator of neurogenesis. To directly investigate the functions of HES-1 in mammalian embryogenesis, we performed a targeted disruption of the HES-1 locus. Mice homozygous for the mutation exhibited severe neurulation defects and died during gestation or just after birth. In the developing brain of HES-1-null embryos, expression of the neural differentiation factor Mash-1 and other neural HLH factors was up-regulated and postmitotic neurons appeared prematurely. These results suggest that HES-1 normally controls the proper timing of neurogenesis and regulates neural tube morphogenesis.
726 citations
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Kobe University1, Gifu University2, University of Tokyo3, Ehime University4, Wakayama Medical University5, Lund University6, Osaka University7, Chinese Academy of Sciences8, Tohoku University9, University of Tokushima10, Kyoto Prefectural University of Medicine11, Kyoto University12, Shiga University of Medical Science13, New Generation University College14, Seoul National University15, The Chinese University of Hong Kong16, University of Helsinki17, Kyushu University18, National Cancer Research Institute19
TL;DR: The data implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries as well as in two independent Japanese populations, and the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of β-cell function or the corrected insulin response.
Abstract: We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest P value (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.
726 citations
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TL;DR: It is shown that serum treatment of cultured cells induces cyclic expression of both mRNA and protein of the Notch effector Hes1, a basic helix-loop-helix (bHLH) factor, with 2-hour periodicity, which may regulate timing in many biological systems.
Abstract: Transcription of messenger RNAs (mRNAs) for Notch signaling molecules oscillates with 2-hour cycles, and this oscillation is important for coordinated somite segmentation. However, the molecular mechanism of such oscillation remains to be determined. Here, we show that serum treatment of cultured cells induces cyclic expression of both mRNA and protein of the Notch effector Hes1, a basic helix-loop-helix (bHLH) factor, with 2-hour periodicity. Cycling is cell-autonomous and depends on negative autoregulation of hes1 transcription and ubiquitin-proteasome-mediated degradation of Hes1 protein. Because Hes1 oscillation can be seen in many cell types, this clock may regulate timing in many biological systems.
726 citations
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TL;DR: Blot and in situ hybridization analyses indicated that mGluR6 mRNA is restrictedly expressed in the inner nuclear layer of the retina where ON-bipolar cells are distributed, and the physiological role of this receptor subtype in the visual system is discussed.
725 citations
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TL;DR: RIG-I is a cytoplasmic sensor of HCV and is governed by RD interactions that are shared with LGP2 as an on/off switch controlling innate defenses, which may have therapeutic implications for immune regulation.
Abstract: RIG-I is an RNA helicase containing caspase activation and recruitment domains (CARDs). RNA binding and signaling by RIG-I are implicated in pathogen recognition and triggering of IFN-alpha/beta immune defenses that impact cell permissiveness for hepatitis C virus (HCV). Here we evaluated the processes that control RIG-I signaling. RNA binding studies and analysis of cells lacking RIG-I, or the related MDA5 protein, demonstrated that RIG-I, but not MDA5, efficiently binds to secondary structured HCV RNA to confer induction of IFN-beta expression. We also found that LGP2, a helicase related to RIG-I and MDA5 but lacking CARDs and functioning as a negative regulator of host defense, binds HCV RNA. In resting cells, RIG-I is maintained as a monomer in an autoinhibited state, but during virus infection and RNA binding it undergoes a conformation shift that promotes self-association and CARD interactions with the IPS-1 adaptor protein to signal IFN regulatory factor 3- and NF-kappaB-responsive genes. This reaction is governed by an internal repressor domain (RD) that controls RIG-I multimerization and IPS-1 interaction. Deletion of the RIG-I RD resulted in constitutive signaling to the IFN-beta promoter, whereas RD expression alone prevented signaling and increased cellular permissiveness to HCV. We identified an analogous RD within LGP2 that interacts in trans with RIG-I to ablate self-association and signaling. Thus, RIG-I is a cytoplasmic sensor of HCV and is governed by RD interactions that are shared with LGP2 as an on/off switch controlling innate defenses. Modulation of RIG-I/LGP2 interaction dynamics may have therapeutic implications for immune regulation.
724 citations
Authors
Showing all 86225 results
Name | H-index | Papers | Citations |
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Kari Alitalo | 174 | 817 | 114231 |
Ralph M. Steinman | 171 | 453 | 121518 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Karl Deisseroth | 160 | 556 | 101487 |
Kenji Kangawa | 153 | 1117 | 110059 |
Takashi Taniguchi | 152 | 2141 | 110658 |
Ben Zhong Tang | 149 | 2007 | 116294 |
Takeo Kanade | 147 | 799 | 103237 |
Yuji Matsuzawa | 143 | 836 | 116711 |
Tasuku Honjo | 141 | 712 | 88428 |
Kenneth M. Yamada | 139 | 446 | 72136 |
Y. B. Hsiung | 138 | 1258 | 94278 |
Shuh Narumiya | 137 | 595 | 70183 |
Kevin P. Campbell | 137 | 521 | 60854 |
Junji Tojo | 135 | 878 | 84615 |