X線回折装置 : 小角散乱<新機種紹介>

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HCV infection activates the proteasome via PA28γ acetylation and heptamerization to facilitate the degradation of RNF2, a catalytic component of polycomb repressive complex 1

We previously reported that hepatitis C virus (HCV) infection or HCV core protein expression induces HOX gene expression by impairing histone H2A monoubiquitination via a proteasome-dependent reduction in the level of RNF2, a key catalytic component of polycomb repressive complex 1 (H. Kasai, K. Mochizuki, T. Tanaka, A. Yamashita, et al., J Virol 95:e01784-20, 2021, https://doi.org/10.1128/jvi.01784-20). In this study, we aimed to investigate the mechanism by which HCV infection accelerates RNF2 degradation. Yeast two-hybrid screening and an immunoprecipitation assay revealed that RNF2 is a PA28γ-binding protein. The proteasome activator PA28γ destabilized the RNF2 protein in a proteasome-dependent manner, since RNF2 degradation was impaired by PA28γ knockout or MG132 treatment. HCV infection or core protein expression reduced the levels of RNF2 and histone H2A K119 monoubiquitination and induced the expression of HOX genes in the presence of PA28γ, while PA28γ knockout reversed these changes. Treatment with a lysine acetyltransferase inhibitor inhibited the acetylation of PA28γ at K195 and the degradation of the RNF2 protein, while treatment with a lysine deacetylase inhibitor accelerated these events in a PA28γ-dependent manner. RNF2 protein degradation was increased by expression of the acetylation mimetic PA28γ mutant but not by expression of the acetylation-defective mutant or the proteasome activation-defective mutant. Furthermore, HCV infection or core protein expression facilitated the interaction between PA28γ and the lysine acetyltransferase CBP/p300 and then accelerated PA28γ acetylation and heptazmerization to promote RNF2 degradation. These data suggest that HCV infection accelerates the acetylation-dependent heptamerization of PA28γ to increase the proteasomal targeting of RNF2

Berberine promotes K48-linked polyubiquitination of HNF4α, leading to the inhibition of HBV replication

The current antiviral agents for the treatment of chronic infection with hepatitis B virus (HBV) do not completely remove covalently closed circular DNA (cccDNA) and integrated viral DNA fragments from patients. Berberine is an isoquinoline alkaloid extracted from various plants and has been reported to inhibit the replication of various types of DNA. In this study, we tested the effects of berberine and its derivatives on HBV infection. Berberine inhibited viral core promoter activity at the highest level among the compounds tested and suppressed HBV production and cccDNA synthesis in primary human hepatocytes and HBV-infected HepG2-NTCP cells at an EC50 value of 3.6 μM and a CC50 value of over 240.0 μM. Compared with other viral promoter activities, berberine treatment potently downregulated core promoter activity and reduced protein levels, but not RNA levels, of hepatic nuclear factor 4α (HNF4α), which primarily enhances enhancer II/core promoter activity. Furthermore, berberine treatment enhanced K48-linked, but not K63-linked, polyubiquitination and subsequent proteasome-dependent degradation of HNF4α. These results suggest that berberine enhances the polyubiquitination- and proteasome-dependent degradation of HNF4α and then inhibits HBV replication via the suppression of core promoter activity. The development of antiviral agents based on berberine may contribute to the amelioration of HBV-related disorders, regardless of the presence of residual cccDNA or integrated viral DNA fragments

Observation of B+→pΛ̅γ

journal articl

生産関数の推定における人的資本の代理変数

2003-03-25The aim of this paper is to examine the role of human capital in the economic growth, emphasizing the choice of proxy for human capital. Though a number of studies have been done on this issue, the results are not consistent with the theory. While a few studies find evidence for productivity of human capital in economic growth, others give different conclusions. We resolve this problem by focusing on possible outliers in sample and measurement error caused by proxy for human capital. Using Japanese cross-section data of 36 regions, we estimate the Benhabib-Spiegel regressions by OLS, LAD and Klepper and Leamer’s reverse regression technique. The main finding is that the human capital proxied by average years of schooling in secondary and higher education have positive effect on economic growth and thus those two variables are the recommendable proxy for human capital.departmental bulletin pape

A global survey of <em>Salmonella</em> plasmids and their associations with antimicrobial resistance

Supplementary Material for ‘A global survey of Salmonella plasmids and their associations with antimicrobial resistance’, as described in Microbial Genomics.</p

Comparative genomic assessment of Multi-Locus Sequence Typing: rapid accumulation of genomic heterogeneity among clonal isolates of -1

Io data has been colour-coded according to data interpretation thresholds described in Taboada . []. Strains showing discordant clustering results are boxed in green.<p><b>Copyright information:</b></p><p>Taken from "Comparative genomic assessment of Multi-Locus Sequence Typing: rapid accumulation of genomic heterogeneity among clonal isolates of "</p><p>http://www.biomedcentral.com/1471-2148/8/229</p><p>BMC Evolutionary Biology 2008;8():229-229.</p><p>Published online 8 Aug 2008</p><p>PMCID:PMC2527321.</p><p></p

Comparative genomic assessment of Multi-Locus Sequence Typing: rapid accumulation of genomic heterogeneity among clonal isolates of -4

Uption of linkage is apparent among members the same CC that share the same loci.<p><b>Copyright information:</b></p><p>Taken from "Comparative genomic assessment of Multi-Locus Sequence Typing: rapid accumulation of genomic heterogeneity among clonal isolates of "</p><p>http://www.biomedcentral.com/1471-2148/8/229</p><p>BMC Evolutionary Biology 2008;8():229-229.</p><p>Published online 8 Aug 2008</p><p>PMCID:PMC2527321.</p><p></p

Comparative genomic assessment of Multi-Locus Sequence Typing: rapid accumulation of genomic heterogeneity among clonal isolates of -3

hyper-variable loci in the genome (B). Mosaicism observed in the CGH data is consistent with that observed in newly sequenced genomes (C). (note: Log Ratio data in (A) and (B) and sequence identity data in (C) were colour coded using a common scale reflecting the likelihood of gene presence/absence).<p><b>Copyright information:</b></p><p>Taken from "Comparative genomic assessment of Multi-Locus Sequence Typing: rapid accumulation of genomic heterogeneity among clonal isolates of "</p><p>http://www.biomedcentral.com/1471-2148/8/229</p><p>BMC Evolutionary Biology 2008;8():229-229.</p><p>Published online 8 Aug 2008</p><p>PMCID:PMC2527321.</p><p></p

Comparative genomic assessment of Multi-Locus Sequence Typing: rapid accumulation of genomic heterogeneity among clonal isolates of -5

boxed in red. Allelic differences with respect to the central sequence type (ST) of the CC are highlighted in blue.<p><b>Copyright information:</b></p><p>Taken from "Comparative genomic assessment of Multi-Locus Sequence Typing: rapid accumulation of genomic heterogeneity among clonal isolates of "</p><p>http://www.biomedcentral.com/1471-2148/8/229</p><p>BMC Evolutionary Biology 2008;8():229-229.</p><p>Published online 8 Aug 2008</p><p>PMCID:PMC2527321.</p><p></p