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Tong Y.-G.,State Key Laboratory of Pathogen and Biosecurity | Shi W.-F.,Institute of Pathogen Biology | Liu D.,CAS Institute of Microbiology | Qian J.,Key Laboratory of Jilin Province for Zoonosis Prevention and Control | And 53 more authors.
Nature | Year: 2015

A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10 â '3 substitutions per site per year (95% highest posterior density interval, 1.04 × 10 â '3 to 1.41 × 10 â '3 substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics. © 2015 Macmillan Publishers Limited. All rights reserved.


Zhang M.-J.,Tianjin University | Zhang M.-J.,Beijing Institute of Radiation Medicine | Ding Y.-L.,Beijing Institute of Radiation Medicine | Ding Y.-L.,State Key Laboratory of Proteomics | And 16 more authors.
FEBS Journal | Year: 2012

Erythroid differentiation-associated gene (EDAG) is a haematopoietic tissue-specific transcription regulator that plays a key role in maintaining the homeostasis of haematopoietic lineage commitment. In acute myeloid leukaemia (AML) patients, the high expression level of EDAG is associated with poor prognosis. NPM1 (nucleophosmin/B23), a ubiquitous nucleolar phosphoprotein, comprises a multifunctional protein that is involved in several cellular processes, including ribosome biogenesis, centrosome duplication, cell cycle progression, cell growth and transformation. Various studies have implicated NPM1 overexpression in promoting tumour cell proliferation, blocking the differentiation of leukaemia cells and resisting apoptosis. In the present study, using co-immunoprecipitation, we characterized EDAG as a physiological binding partner of NPM1; The N-terminal (amino acids 1-124) region of EDAG interacts with the N-terminal (amino acids 118-187) of NPM1. Under cycloheximide treatment, the stability of NPM1 protein was enhanced by EDAG overexpression, whereas knockdown of EDAG by lentivirus-mediated small interfering RNA resulted in an increased degradation rate of NPM1 in K562 cells. During 4β-phorbol l2-myristate 13-acetate-induced K562 megakaryocytic differentiation, overexpression of EDAG prevented the down-regulation of NPM1 proteins, whereas knockdown of EDAG accelerated the down-regulation of NPM1. EDAG deletion mutant lacking the binding domain with NPM1 lost the ability to stabilize NPM1 protein. Furthermore, knockdown of EDAG in K562 cells led to increased cell apoptosis induced by imatinib, and re-expression of NPM1 attenuated the increased apoptosis. These results suggest that EDAG enhances the protein stability of NPM1 via binding to NPM1, which plays a critical role in the anti-apoptosis of leukaemia cells. © 2012 FEBS.


Ding Y.-L.,Beijing Institute of Radiation Medicine | Xu C.-W.,Beijing Institute of Radiation Medicine | Wang Z.-D.,Beijing Institute of Radiation Medicine | Zhan Y.-Q.,Beijing Institute of Radiation Medicine | And 12 more authors.
Journal of Cellular Biochemistry | Year: 2010

Erythroid differentiation-associated gene (EDAG), a hematopoietic tissue-specific transcription regulator, plays a key role in maintaining the homeostasis of hematopoietic lineage commitment. However, the mechanism and genes regulated by EDAG remain unknown. In this study, we showed that overexpression of EDAG in a myeloid cell line 32D led to an erythroid phenotype with increased number of benzidine-positive cells and up-regulation of erythroid specific surface marker TER119. The megakaryocytic specific marker CD61 was also induced significantly. Using a genome-wide microarray analysis and a twofold change cutoff, we identified 332 genes with reduced expression and 288 genes with increased expression. Among up-regulation genes, transcription factor GATA-1 and its target genes including EKLF, NF-E2, Gfi-1b, hemogen, SCL, hemoglobin alpha, beta and megakaryocytic gene GPIX were increased. Silencing of EDAG by RNA interference in K562 cells resulted in down-regulation of these genes. Taken together, EDAG functions as a positive regulator of erythroid/megakaryocytic differentiation in 32D cells associated with the induction of GATA-1 and its target genes. © 2010 Wiley-Liss, Inc.


Li C.-Y.,Beijing Institute of Radiation Medicine | Cao C.-Z.,Beijing Institute of Radiation Medicine | Xu W.-X.,State Key Laboratory of Proteomics | Cao M.-M.,Tianjin University | And 12 more authors.
Gut | Year: 2010

Background: Human hepassocin (HPS) was originally detected by subtractive and differential cDNA cloning as a liver-specific gene that was markedly upregulated during liver regeneration. Previous studies suggested that HPS showed mitogenic activity on isolated hepatocytes in vitro. However, its in vivo functions remained largely unknown. Therefore, the function of recombinant human HPS during liver regeneration and chemically induced liver injury was investigated. Methods: The proliferation of primary hepatocytes was examined by [3H]thymidine incorporation and immunohistological staining of proliferating cell nuclear antigen (PCNA). RNA interference was performed to knock down the endogenous expression of HPS. The proliferation of L02 cells was examined by MTS assay. The phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1/2) was investigated by western blotting analysis. Assessment of liver injury (histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels) and of apoptosis, by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, was performed. Results: Purified recombinant human HPS showed specific mitogenic activity on primary hepatocytes and normal liver cell lines in a mitogen-activated protein kinase (MAPK)-dependent manner and stimulated the proliferation of hepatocytes in rats with 70% partial hepatectomy. Administration of HPS to rats after D-galactose and carbon tetrachloride (CCl4) treatment protected against liver injury (minimal liver necrosis, depressed ALT and AST levels, and decreased lethality), reduced apoptosis and enhanced proliferation. Knock-down of endogenous HPS in vivo enhanced the liver injury induced by D-galactose by increasing the apoptosis and elevating ALT and AST levels. Conclusions: HPS is a hepatic growth factor which can accelerate hepatocyte proliferation in vivo and protect against liver injury. These data point to the potential interest of HPS in the treatment of fulminant hepatic failure.


Lian W.-X.,Anhui Medical University | Lian W.-X.,Beijing Institute of Radiation Medicine | Yin R.-H.,Beijing Institute of Radiation Medicine | Kong X.-Z.,Beijing Institute of Radiation Medicine | And 18 more authors.
FEBS Letters | Year: 2012

THAP11 is an essential factor involved in ES cell pluripotency and cell growth. Here, we identified THAP11 as a novel physiological binding partner of PCBP1. In HepG2 cells, THAP11 overexpression inhibited CD44 v6 expression and cell invasion. However, when deleting the binding domain with PCBP1 or endogenous PCBP1 was knocked down, THAP11 failed to inhibit CD44 v6 expression, indicating that THAP11 regulates CD44 v6 expression through interacting with PCBP1. In HCC patients, the expression of THAP11 mRNA significantly correlated with PCBP1 mRNA expression. Our results suggest a novel role of THAP11 in CD44 alternative splicing and hepatoma invasion. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Gao M.,Tianjin University | Gao M.,Beijing Institute of Radiation Medicine | Zhan Y.-Q.,Beijing Institute of Radiation Medicine | Zhan Y.-Q.,State Key Laboratory of Proteomics | And 14 more authors.
Cellular Signalling | Year: 2014

Hepassocin (HPS) is a secreted protein with mitogenic activity on primary hepatocytes and protects hepatocytes from chemically-induced injury. Our previous studies showed that HPS stimulates proliferation of hepatocytes in an ERK pathway-dependent manner. However, the molecular mechanism of HPS-induced activation of the ERK pathway remains unclear. In this study, we found that HPS induced the phosphorylation of the epidermal growth factor receptor (EGFR) in the human L02 hepatocyte cell line, and this event was concomitant with the activation of the non-receptor tyrosine kinase Src. Specific inhibition of EGFR kinase activity by gefitinib or down-regulation of EGFR by specific EGFR siRNAs prevented HPS-induced activation of the ERK pathway and proliferation of L02 cells. Furthermore, inhibition of Src activity significantly blocked HPS-induced activation of the EGFR, which was suggestive of a ligand-independent transactivation mechanism of EGFR itself as well as ERK phosphorylation and proliferation of L02 cells. These results indicate that EGFR plays an important role in the mitogenic signaling induced by HPS in L02 cell lines and may further stimulate research on the role of HPS in hepatocytes within biological processes in human health and disease. © 2014 Elsevier Inc.


Zheng W.-W.,Beijing Institute of Radiation Medicine | Yang Y.,Purdue University | Zhang M.-J.,Tianjin University | Dong X.-M.,Beijing University of Technology | And 10 more authors.
Progress in Biochemistry and Biophysics | Year: 2013

Nucleophosmin (NPM1 or B23.1) is a ubiquitously expressed nuclear phosphoprotein that plays key role in several cellular processes, including ribosome biogenesis, centrosome duplication, cell cycle progression, cell growth, and transformation. NPM1 is one of the most frequently mutated genes in AML. EDAG is a hematopoietic tissue-specific transcription regulator that plays a key role in maintaining the homeostasis of hematopoietic lineage commitment. In AML patients, the high expression level of EDAG is associated with poor prognosis. Our previous study suggest that EDAG is a physiological binding partner of NPM1 and regulates NPM1 protein stability, however, whether EDAG regulates NPM1 in AML patients and whether EDAG regulates NPM1 mutations remain unknown. In the present study, we found that in bone marrow CD34+ cells from AML patients, silencing of EDAG led to decreased protein stability of NPM1 protein and increased cell sensitivity to daunorubicin. Although EDAG failed to interact with NPMc+ and regulate its protein stability in normal culture condition, with leptomycin B treatment, EDAG overexpression enhanced the protein stability of NPMc+. In AML patients with NPMc+, the CD34 cells were more responsive to daunorubicin treatment than the cells from AML with wild type NPM1, and silencing of EDAG weakly increased the sensitivity to daunorubicin. These results suggested a potential role of EDAG in chemotherapy of AML and the "escape" of NPMc + protein from EDAG stabilization might contribute to the favorable prognosis of AML with NPMc+.


Chen T.,National University of Defense Technology | Chen T.,Beijing Institute of Radiation Medicine | Chen T.,State Key Laboratory of Proteomics | Chen T.,Beijing Proteome Research Center | And 2 more authors.
Ruan Jian Xue Bao/Journal of Software | Year: 2013

Object-Based storage is a good choice for large scale storage systems. Load balancing of metadata is important to improve the performance of I/O. The existing load balancing schemas cannot evenly distribute the accesses of metadata in a dynamic way. Moreover, the adaptability and fault-tolerance ability need to be improved. This paper presents an adaptable distributed load balancing of metadata (ADMLB) which is composed of basic load balancing algorithm (BBLA) and distributed incremental load balancing algorithm (IBLA). Specially, ADMLB first uses BBLA to distribute metadata loads according to the performances of the metadata servers and then uses IBLA to incrementally reorganize loads on each metadata server. ADMLB can evenly distribute loads between metadata servers and adapts well to the changes of loads. It also has good fault-tolerance ability, and locates metadata servers very quickly. ©2013 ISCAS.


Cao M.-M.,Tianjin University | Cao M.-M.,Beijing Institute of Radiation Medicine | Xu W.-X.,Beijing Institute of Radiation Medicine | Li C.-Y.,Beijing Institute of Radiation Medicine | And 16 more authors.
Journal of Cellular Biochemistry | Year: 2011

Hepassocin (HPS) is a specific mitogenic active factor for hepatocytes, and inhibits growth by overexpression in hepatocellular carcinoma (HCC) cells. However, the mechanism of HPS regulation on growth of liver-derived cells still remains largely unknown. In this study, we found that HPS was expressed and secreted into the extracellular medium in cultured L02 human hepatic cells; conditional medium of L02 cells promoted proliferation of L02 cells and this activity could be blocked by anti-HPS antibody. Moreover, we identified the presence of receptor for HPS on L02 cells and HepG2 human hepatoma cells. Overproduction of truncated HPS, which signal peptide was deleted, significantly inhibited the proliferation of HCC cells and induced cell cycle arrest. These findings suggest that HPS promotes hepatic cell line L02 cells proliferation via an autocrine mechanism and inhibits HCC cells proliferation by an intracrine pathway. Copyright © 2011 Wiley-Liss, Inc.

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