Differential expression of extracellular-signal-regulated kinase 5 (ERK5) in normal and degenerated human nucleus pulposus tissues and cells

Extracellular-signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and regulates a wide variety of cellular processes such as proliferation, differentiation, necrosis, apoptosis and degeneration. However, the expression of ERK5 and its role in degenerated human nucleus pulposus (NP) is hitherto unknown. In this study, we observed the differential expression of ERK5 in normal and degenerated human nucleus pulposus tissues by using immunohistochemical staining and Western blot. Treatment of NP cells with Pro-inflammatory cytokine, TNF-α decreased ERK5 gene expression as well as NP marker gene expression; including the type II collagen and aggrecan. Suppression of ERK5 gene expression in NP cells by ERK5 siRNA resulted in decreased gene expression of type II collagen and aggrecan. Furthermore, inhibition of ERK5 activation by BIX02188 (5 μM) decreased the gene expression of type II collagen and aggrecan in NP cells. Our results document the expression of ERK5 in degenerated nucleus pulposus tissues, and suggest a potential involvement of ERK5 in human degenerated nucleus pulposus.     

Surface Reconstruction through Poisson Disk Sampling

This paper intends to generate the approximate Voronoi diagram in the geodesic metric for some unbiased samples selected from original points. The mesh model of seeds is then constructed on basis of the Voronoi diagram. Rather than constructing the Voronoi diagram for all original points, the proposed strategy is to run around the obstacle that the geodesic distances among neighboring points are sensitive to nearest neighbor definition. It is obvious that the reconstructed model is the level of detail of original points. Hence, our main motivation is to deal with the redundant scattered points. In implementation, Poisson disk sampling is taken to select seeds and helps to produce the Voronoi diagram. Adaptive reconstructions can be achieved by slightly changing the uniform strategy in selecting seeds. Behaviors of this method are investigated and accuracy evaluations are done. Experimental results show the proposed method is reliable and effective.     

Targeting Mcl-1 for Radiosensitization of Pancreatic Cancers

In order to identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer, we previously conducted an RNAi library screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1), an anti-apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic cancer cells to chemoradiation. In the present study we investigated Mcl-1 inhibition by either genetic or pharmacological approaches as a radiosensitizing strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA produced significant radiosensitization in BxPC-3 and Panc-1 cells in association with Caspase-3 activation and PARP cleavage, but only minimal radiosensitization in MiaPaCa-2 cells. We next tested the ability of the recently identified, selective, small molecule inhibitor of Mcl-1, UMI77, to radiosensitize in pancreatic cancer cells. UMI77 caused dissociation of Mcl-1 from the pro-apoptotic protein Bak and produced significant radiosensitization in BxPC-3 and Panc-1 cells, but minimal radiosensitization in MiaPaCa-2 cells. Radiosensitization by UMI77 was associated with Caspase-3 activation and PARP cleavage. Importantly, UMI77 did not radiosensitize normal small intestinal cells. In contrast, ABT-737, an established inhibitor of Bcl-2, Bcl-X_L, and Bcl-w, failed to radiosensitize pancreatic cancer cells suggesting the unique importance of Mcl-1 relative to other Bcl-2 family members to radiation survival in pancreatic cancer cells. Taken together, these results validate Mcl-1 as a target for radiosensitization of pancreatic cancer cells and demonstrate the ability of small molecules which bind the canonical BH3 groove of Mcl-1, causing displacement of Mcl-1 from Bak, to selectively radiosensitize pancreatic cancer cells.     

FERONIA Receptor Kinase Controls Seed Size in Arabidopsis thaliana

Dear Editor,
Plants have evolved elaborate mechanisms by which cell elongation regulation is coupled to the environmental signals. The plasma membrane receptor kinase FERONIA （FER） has emerged as an important regulatory node in controlling cell elongation and hormone crosstalk （Guo et al., 2009; Deslauriers and Larsen, 2010; Duan et al., 2010; Yu et al.,     

Mimotopes selected with neutralizing antibodies against multiple subtypes of influenza A

Background

The mimotopes of viruses are considered as the good targets for vaccine design. We prepared mimotopes against multiple subtypes of influenza A and evaluate their immune responses in flu virus challenged Balb/c mice.

Methods

The mimotopes of influenza A including pandemic H1N1, H3N2, H2N2 and H1N1 swine-origin influenza virus were screened by peptide phage display libraries, respectively. These mimotopes were engineered in one protein as multi- epitopes in Escherichia coli (E. coli) and purified. Balb/c mice were immunized using the multi-mimotopes protein and specific antibody responses were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). The lung inflammation level was evaluated by hematoxylin and eosin (HE).

Results

Linear heptopeptide and dodecapeptide mimotopes were obtained for these influenza virus. The recombinant multi-mimotopes protein was a 73 kDa fusion protein. Comparing immunized infected groups with unimmunized infected subsets, significant differences were observed in the body weight loss and survival rate. The antiserum contained higher HI Ab titer against H1N1 virus and the lung inflammation level were significantly decreased in immunized infected groups.

Conclusions

Phage-displayed mimotopes against multiple subtypes of influenza A were accessible to the mouse immune system and triggered a humoral response to above virus.

     

The L60V Variation in Hepatitis B Virus Core Protein Elicits New Epitope-Specific Cytotoxic T Lymphocytes and Enhances Viral Replication

Mutations in the core protein (HBc) of hepatitis B virus (HBV) are associated with aggressive hepatitis and advanced liver diseases in chronic hepatitis B (CHB). In this study, we identified the L60V variation in HBc that generates a new HLA-A2-restricted CD8⁺ T cell epitope by screening an overlapping 9-mer peptide pool covering HBc and its variants. The nonameric epitope V60 was determined by structural and immunogenic analysis. The HBc L60V variation is correlated with hepatic necroinflammation and higher viral levels, and it may be associated with a poor prognosis in CHB patients. Immunization with the defined HBV epitope V60 peptide elicited specific cytotoxic T lymphocyte (CTL)-induced liver injury in HLA-A2⁺ HBV transgenic mice. In addition, in vitro and in vivo experiments both demonstrated that the HBc L60V variation facilitates viral capsid assembly and increases HBV replication. These data suggest that the HBc L60V variation can impact both HBV replication and HBV-specific T cell responses. Therefore, our work provides further dissection of the impact of the HBc L60V variation, which orchestrates HBV replication, viral persistence, and immunopathogenesis during chronic viral infection.     

中国特有种云南圆口藓的修订和新分布区报道

通过查看模式标本和普通标本,对中国特有种——云南圆口藓进行了修订。据模式特征,重新订正了中国各地标本,确定本种分布在中国云南、辽宁和内蒙古,其中内蒙古为新分布区。除描述和讨论外,还就模式标本绘制了各种特征的解剖图,根据普通标本进行了显微拍照,以补现有文献形态描述和绘图的不足。     

牛大力淀粉酶基因家族的生物信息学分析

该文基于不膨大和膨大的牛大力根的转录组测序结果,采用生物信息学技术对筛选到的28个牛大力淀粉酶基因进行分析。结果表明:28个牛大力淀粉酶相关蛋白基因编码的氨基酸序列分子量为20.78～349.39 KDa;均为酸性蛋白部分;部分亚细胞定位在叶绿体;具有PLN02784 super family、AmyAc-family super family结构域;二级结构中除MsAm1、MsAm7、MsAm8、MsAm15、MsAm16、MsAm22、MsAm23、MsAm28中α螺旋占比最大外,无规则卷曲的比例最大;三级结构预测具有α淀粉酶结构、β淀粉酶结构、异淀粉酶结构等;淀粉酶基因家族共有86个作用元件,MsAm9的作用元件最多(42个);系统发育树表明MsAm15、MsAm16归于1类,且均具有motif 2、motif 3、motif 7,MsAm4、MsAm24、MsAm26归于1类,与拟南芥淀粉酶进行比对,AtBM4和MsAm6归为一类,AtAM2和MsAm2归为一类,AtBM8和MsAm5归为一类,AtBM4和MsAm6归为一类,AtAM10和MsAm22归为一类,AtIM3和Ms...