PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer

Lee, K-H,Park, J-W,Sung, H-S,Choi, Y-J,Kim, W H,Lee, H S,Chung, H-J,Shin, H-W,Cho, C-H,Kim, T-Y,Li, S-H,Youn, H-D,Kim, S J,Chun, Y-S Macmillan Publishers Limited 2015 Oncogene Vol.34 No.22

Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.

c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of the TGF-β Type II Receptor

Zuo, W.,Huang, F.,Chiang, Y.,Li, M.,Du, J.,Ding, Y.,Zhang, T.,Lee, H.,Jeong, L.,Chen, Y.,Deng, H.,Feng, X.H.,Luo, S.,Gao, C.,Chen, Y.G. Cell Press 2013 Molecular cell Vol.49 No.3

Transforming growth factor β (TGF-β) is a potent antiproliferative factor in multiple types of cells. Deregulation of TGF-β signaling is associated with the development of many cancers, including leukemia, though the molecular mechanisms are largely unclear. Here, we show that Casitas B-lineage lymphoma (c-Cbl), a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-β signaling by neddylating and stabilizing the type II receptor (TβRII). Knockout of c-Cbl decreases the TβRII protein level and desensitizes hematopoietic stem or progenitor cells to TGF-β stimulation, while c-Cbl overexpression stabilizes TβRII and sensitizes leukemia cells to TGF-β. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TβRII at Lys556 and Lys567. Neddylation of TβRII promotes its endocytosis to EEA1-positive early endosomes while preventing its endocytosis to caveolin-positive compartments, therefore inhibiting TβRII ubiquitination and degradation. We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant TβRII neddylation and leukemia development.

Electrolyte effect on the catalytic performance of Ni-based catalysts for direct internal reforming molten carbonate fuel cell

Li, Z.,Devianto, H.,Yoon, S.P.,Han, J.,Lim, T.H.,Lee, H.I. Pergamon Press ; Elsevier Science Ltd 2010 International journal of hydrogen energy Vol.35 No.23

An active and tolerant Ni-based catalyst for methane steam reforming in direct internal reforming molten carbonate fuel cells (DIR-MCFCs) was developed. Deactivation of reforming catalysts by alkali metals from the electrolyte composed of Li<SUB>2</SUB>CO<SUB>3</SUB> and K<SUB>2</SUB>CO<SUB>3</SUB> is one of the major obstacles to be overcome in commercialization of DIR-MCFCs. Newly developed Ni/MgSiO<SUB>3</SUB> and Ni/Mg<SUB>2</SUB>SiO<SUB>4</SUB> reforming catalysts show activities of ca. 80% methane conversion. Subsequent to electrolyte addition to the catalyst, however, the activity of Ni/Mg<SUB>2</SUB>SiO<SUB>4</SUB> decreases to ca. 50% of its initial value, whereas Ni/MgSiO<SUB>3</SUB> catalyst retains its initial activity. Results obtained from temperature-programmed reduction and X-ray photoelectron spectroscopy identify unreduced Ni<SUP>3+</SUP> as a decisive factor in keeping catalytic activity from the electrolyte.

Mucosally administered Lactobacillus surface-displayed influenza antigens (sM2 and HA2) with cholera toxin subunit A1 (CTA1) Induce broadly protective immune responses against divergent influenza subtypes

Li, R.,Chowdhury, M.Y.E.,Kim, J.H.,Kim, T.H.,Pathinayake, P.,Koo, W.S.,Park, M.E.,Yoon, J.E.,Roh, J.B.,Hong, S.P.,Sung, M.H.,Lee, J.S.,Kim, C.J. Elsevier Scientific Pub. Co 2015 Veterinary microbiology Vol.179 No.3

The development of a universal influenza vaccine that provides broad cross protection against existing and unforeseen influenza viruses is a critical challenge. In this study, we constructed and expressed conserved sM2 and HA2 influenza antigens with cholera toxin subunit A1 (CTA1) on the surface of Lactobacillus casei (pgsA-CTA1sM2HA2/L. casei). Oral and nasal administrations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and their isotypes (IgG1 & IgG2a) as well as mucosal IgA. The mucosal administration of pgsA-CTA1sM2HA2/L. casei may also significantly increase the levels of sM2- or HA2-specific cell-mediated immunity because increased release of both IFN-γ and IL-4 was observed. The recombinant pgsA-CTA1sM2HA2/L. casei provided better protection of BALB/c mice against 10 times the 50% mouse lethal doses (MLD<SUB>50</SUB>) of homologous A/EM/Korea/W149/06(H5N1) or A/Aquatic bird/Korea/W8½005 (H5N2) and heterologous A/Puerto Rico/8/34(H1N1), or A/Chicken/Korea/116/2004(H9N2) or A/Philippines/2/08(H3N2) viruses, compared with L. casei harboring sM2HA2 and also the protection was maintained up to seven months after administration. These results indicate that recombinant L. casei expressing the highly conserved sM2, HA2 of influenza and CTA1 as a mucosal adjuvant could be a potential mucosal vaccine candidate or tool to protect against divergent influenza viruses for human and animal.

Vector prime protein boost vaccination in the setting of myeloablative-induced lymphopenia suppresses growth of leukemia and solid tumors

Han, T H,Tang, Y,Park, Y H,Maynard, J,Li, P,Akbulut, H,Petersen, L,Deisseroth, A Macmillan Publishers Limited 2010 Bone marrow transplantation Vol.45 No.3

We have developed a vaccine, which is designed to induce tumor-associated antigen (TAA)-specific T cells and antibodies in the setting of profound lymphopenia induced by myeloablative therapy and T-cell-depleted bone marrow transplantation. Test mice were injected subcutaneously (sc) with the 32DP210Bcr-Abl cell line, which is positive for the p210Bcr-Abl protein (Group 1). In Group 2, 7 days after injection of the 32DP210Bcr-Abl positive cell line, the mice received 900 cGy total body irradiation (TBI) followed in 1 h by the intravenous infusion of 10 million T-cell-depleted syngeneic bone marrow cells (TCDBMT) (Group 2). The leukemia-bearing group received an intravenous injection of 10 million spleen cells (donor lymphocyte infusions) from unvaccinated (Group 3) and TAA/ecdCD40L-vaccinated (Group 4) syngeneic mice 3 days after completion of the TBI and TCDBMT. Groups 3 and 4 mice received three additional sc vaccinations at 7-day intervals with the TAA/ecdCD40L vaccine, in which the TAA was taken from the junctional peptide of the P210bcr-Abl protein. The survival of Groups 3 and 4 mice was significantly longer than that in Groups 1 and 2 mice. Vaccinated mice from Group 4, which developed complete responses, survived up to 350 days post-injection of the leukemia cells without any evidence of leukemia regrowth.

Coronary Atherosclerosis T₁-Weighed Characterization With Integrated Anatomical Reference

Xie, Y.,Kim, Y.J.,Pang, J.,Kim, J.S.,Yang, Q.,Wei, J.,Nguyen, C.T.,Deng, Z.,Choi, B.W.,Fan, Z.,Bairey Merz, C.N.,Shah, P.K.,Berman, D.S.,Chang, H.J.,Li, D. Elsevier Science B.V. Amsterdam 2017 JACC CARDIOVASCULAR IMAGING Vol.10 No.6

Objectives: The aim of this work is the development of coronary atherosclerosis T<SUB>1</SUB>-weighted characterization with integrated anatomical reference (CATCH) technique and the validation by comparison with high-risk plaque features (HRPF) observed on intracoronary optical coherence tomography (OCT) and invasive coronary angiography. Background: T<SUB>1</SUB>-weighted cardiac magnetic resonance with or without contrast media has been used for characterizing coronary atherosclerosis showing promising prognostic value. Several limitations include: 1) coverage is limited to proximal coronary segments; 2) spatial resolution is low and often anisotropic; and 3) a separate magnetic resonance angiography acquisition is needed to localize lesions. Methods: CATCH acquired dark-blood T<SUB>1</SUB>-weighted images and bright-blood anatomical reference images in an interleaved fashion. Retrospective motion correction with 100% respiratory gating efficiency was achieved. Reference control subjects (n = 13) completed both pre- and post-contrast scans. Stable angina patients (n = 30) completed pre-contrast scans, among whom 26 eligible patients also completed post-contrast scans. After cardiac magnetic resonance, eligible patients (n = 22) underwent invasive coronary angiography and OCT for the interrogation of coronary atherosclerosis. OCT images were assessed and scored for HRPF (lipid-richness, macrophages, cholesterol crystals, and microvessels) by 2 experienced analysts blinded to magnetic resonance results. Results: Per-subject analysis showed none of the 13 reference control subjects had coronary hyperintensive plaques (CHIP) in either pre-contrast or post-contrast CATCH. Five patients had CHIP on pre-contrast CATCH and 5 patients had CHIP on post-contrast CATCH. Patients with CHIP had greater lipid abnormality than those without. Per-segment analysis showed elevated pre- and post-contrast plaque to myocardium signal ratio in the lesions with HRPF versus those without. Positive correlation was observed between plaque to myocardium signal ratio and OCT HRPF scoring. CHIP on pre-contrast CATCH were associated with significantly higher stenosis level than non-CHIP on invasive coronary angiography. Conclusions: CATCH provided accelerated whole heart coronary plaque characterization with simultaneously acquired anatomical reference. CHIP detected by CATCH showed positive association with high-risk plaque features on invasive imaging studies.

Antiviral activities of compounds from aerial parts of Salvia plebeia R. Br

Bang, S.,Quy Ha, T.K.,Lee, C.,Li, W.,Oh, W.K.,Shim, S.H. Elsevier Sequoia 2016 Journal of Ethnopharmacology Vol.192 No.-

Ethnopharmacological relevance: Salvia plebeia R. Br. is an edible plant widely spread in many countries. It has been used as a traditional medicine to treat common cold, flu, cough, hepatitis, hemorrhoids, etc. The purpose of the study is to explicate antiviral compounds responsible for its traditional use for the common cold or flu. Materials and methods: The methanolic extract of the aerial parts of S. plebeia was extracted with CHCl<SUB>3</SUB>, EtOAc, and n-BuOH, successively. The EtOAc and CHCl<SUB>3</SUB> fractions were subjected to a successive of chromatographic method, which led to the isolation of fourteen compounds. Inhibition activities of the isolated compounds were evaluated against influenza A (H1N1) neuraminidase. Results: Chemical investigation of the methanolic extracts of S. plebeia resulted in the isolation of two novel benzoylated monoterpene glycosides, named as plebeiosides A (1) and B (2), together with twelve known compounds including four flavonoids (4-5, 7, 10), two sesquiterpenoids (8, 12), four phenolics (9-10, 13-14), a steroid (6), and a triterpenoid (3). Their chemical structures were elucidated based on spectroscopic data and absolute stereochemistries of 1 and 2 were determined by comparison of optical rotations of their hydrolysates with literature values. Compounds 5, 7, 9, and 11 exhibited potent enzymatic inhibition against H1N1 neuraminidase (IC<SUB>50</SUB> values ranging from 11.18+/-1.73 to 19.83+/-2.28μM). Furthermore, two flavonoids (5 and 7) and one rosmarinic acid methyl ester (9) reduced cytopathic effects of the H1N1 virus during replication. Conclusions: The antiviral activities of the flavonoids and phenolics isolated from the extracts of S. plebeia supported the traditional application of this medicine on common cold or flu. In this study, benzoylated monoterpene glycosides were first found to exist in this species. Moreover, the present study suggested potential of three compounds (5, 7, and 9) to be new lead structures for the development of new neuraminidase inhibitors in the future.

China Spallation Neutron Source: Accelerator Design Iterations and R&D Status

J. Wei,C.-D. Deng,C.-H. Wang,C.-T. Shi,H. Sun,H.-F. Ouyang,H.-M. Qu,H.-Y. Dong,J. Li,J. Zhang,J.-S. Cao,J.-Y. Tang,L. Dong,L.-L. Wang,Q. Qin,Q.-B. Wang,S. Wang,S.-N. Fu,S.-X Fang,T. -G. Xu,W. Kang,Y.- 한국물리학회 2007 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.50 No.I

The China Spallation Neutron Source (CSNS) is a high-power, accelerator-based project currently under preparation. The accelerator complex consists of an H$^-$ ion source, an H$^-$ linac, a rapid-cycling proton synchrotron, and the transport lines. During the past year, the design of most accelerator systems went through major iterations, and initial research and developments was started on the prototyping of several key components.

하이브리드 다층 인쇄회로기판의 굽힘 강도 개선에 관한 해석 및 실험적 연구

Le Li,김상목(S.M. Kim),송승호(S.H. Song),구태완(T.W. Ku),송우진(W.J. Song),김정(J. Kim),강범수(B.S. Kang) 한국정밀공학회 2007 한국정밀공학회 학술발표대회 논문집 Vol.2007 No.11월

Investigation of PCR-RFLPs within Major Histocompatibility Complex B-G Genes Using Two Restriction Enzymes in Eight Breeds of Chinese Indigenous Chickens

R. F. Xu,K. Li,G. H. Chen,B. Y. Z. Qiang,D. L. Mo,B. Fan,C. C. Li,M. Yu,M. J. Zhu,T. A. Xiong,B. Liu 아세아·태평양축산학회 2005 Animal Bioscience Vol.18 No.7

New polymorphism of major histocompatibility complex B-G genes was investigated by amplification and digestion of a 401bp fragment including intron 1 and exon 2 using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique with two restriction enzymes of Msp I and Tas I in eight breeds of Chinese indigenous chickens and one exotic breed. In the fragment region of the gene, three novel single nucleotide polymorphisms (SNPs) were detected at the two restriction sites. We found the transition of two nucleotides of A294G and T295C occurred at Tas I restriction site, and consequently led to a nonsynonymous substitution of asparagine into serine at position 54 within the deduced amino acid sequence of immunoglobulin variableregion- like domain encoded by the exon 2 of B-G gene. It was observed at rare frequency that a single mutation of A294G occurring at the site, also caused an identical substitution of amino acid, asparagine 54-to-serine, to that we described previously. And the transversion of G319C at Msp I site led to a non-synonymous substitution, glutamine 62-to-histidine. The new alleles and allele frequencies identified by the PCR-RFLP method with the two enzymes were characterized, of which the allele A and B frequencies at Msp I and Tas I loci were given disequilibrium distribution either in the eight Chinese local breeds or in the exotic breed. By comparison, allele A at Msp I locus tended to be dominant, while, the allele B at Tas I locus tended to be dominant in all of the breeds analyzed. In Tibetan chickens, the preliminary association analysis revealed that no significant difference was observed between the different genotypes identified at the Msp I and Tas I loci and the laying performance traits, respectively.