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1. chinaXiv:201605.01726 [pdf]

The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold

Wan, Zhengpeng; Chen, Xiangjun; Chen, Yingjia; Wang, Jing; Cao, Yiyun; Liu, Wanli; Chen, Haodong; Wang, Fei; Tang, Zhuo; Ji, Qinghua; Lou, Jizhong
Subjects: Biology >> Biophysics >> Biology

B lymphocytes use B cell receptors (BCRs) to sense the physical features of the antigens. However, the sensitivity and threshold for the activation of BCRs resulting from the stimulation by mechanical forces are unknown. Here, we addressed this question using a double-stranded DNA-based tension gauge tether system serving as a predefined mechanical force gauge ranging from 12 to 56 pN. We observed that IgM-BCR activation is dependent on mechanical forces and exhibits a multi-threshold effect. In contrast, the activation of isotype-switched IgG- or IgE-BCR only requires a low threshold of less than 12 pN, providing an explanation for their rapid activation in response to antigen stimulation. Mechanistically, we found that the cytoplasmic tail of the IgG-BCR heavy chain is both required and sufficient to account for the low mechanical force threshold. These results defined the mechanical force sensitivity and threshold that are required to activate different isotyped BCRs.

submitted time 2016-05-15 Hits754Downloads441 Comment 0

2. chinaXiv:201605.01472 [pdf]

Antigenic variation of the human influenza A (H3N2) virus during the 2014-2015 winter season

Hua Sha; Liu Mi; Wu AiPing; Jiang TaiJiao; Hua Sha; Liu Mi; Li XiYan; Cheng YanHui; Huang WeiJuan; Tan MinJu; Wei HeJiang; Guo JunFeng; Wang DaYan; Shu YueLong; Peng YouSong; Jiang TaiJiao; Wu AiPing; Jiang TaiJiao; Wu AiPing; Jiang TaiJiao
Subjects: Biology >> Biophysics >> Biology

The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many countries and caused massive morbidity and mortality because of its antigenic variation. So far, very little is known about the antigenic patterns of the recent H3N2 virus. By systematically mapping the antigenic relationships of H3N2 strains isolated since 2010, we discovered that two groups with obvious antigenic divergence, named SW13 (A/Switzerland/9715293/2013-like strains) and HK14 (A/Hong Kong/5738/2014-like strains), co-circulated during the 2014-2015 winter season. HK14 group co-circulated with SW13 in Europe and the United States during this season, while there were few strains of HK14 in mainland China, where SW13 has dominated since 2012. Furthermore, we found that substitutions near the receptor-binding site on hemagglutinin played an important role in the antigenic variation of both the groups. These findings provide a comprehensive understanding of the recent antigenic evolution of H3N2 virus and will aid in the selection of vaccine strains.

submitted time 2016-05-12 Hits710Downloads457 Comment 0

3. chinaXiv:201605.01447 [pdf]

The conformational states of talin autoinhibition complex and its activation under forces

Zeng Yan; Zhang Yong; Ji QingHua; Lou JiZhong; Song XianQiang; Ye Sheng; Zhang RongGuang; Zeng Yan; Song XianQiang; Ji QingHua
Subjects: Biology >> Biophysics >> Biology

Talin is an integrin-binding protein located at focal adhesion site and serves as both an adapter and a force transmitter. Its integrin binding activity is regulated by the intramolecular autoinhibition interaction between its F3 and RS domains. Here, we used atomic force microscopy to measure the strength of talin autoinhibition complex. Our results suggest that the lifetime of talin autoinhibition complex shows weak catch bond behavior and does not change significantly at smaller forces, while it drops rapidly at larger forces (>10 pN). Moreover, besides the complex conformation revealed by crystal structure, our molecular dynamics (MD) simulations indicate the possible existence of another stable conformation. Further analysis indicates that forces may regulate the equilibrium of the two stable binding states and result in the non-exponential force dependence of the binding lifetime. Our findings reveal a negative regulation mechanism on talin activation and provide a new point of view on the function of talin in focal adhesion.

submitted time 2016-05-12 Hits717Downloads423 Comment 0

4. chinaXiv:201605.01421 [pdf]

The Effect of Ionizing Radiation on mRNA Levels of the DNA Damage Response Genes Rad9, Rad1 and Hus1 in Various Mouse Tissues

Zhang, Zhenya; Li, Kaiming; Cai, Zeyuan; Fang, Yu; An, Lili; Hu, Zhishang; Hang, Haiying; Cai, Zeyuan; Hu, Zhishang
Subjects: Biology >> Biophysics >> Biology

Rad9, Rad1 and Hus1 are essential genes conserved from yeast to humans. They form a heterotrimer complex (9-1-1 complex) that participates in the cell cycle checkpoint activation and DNA damage repair in eukaryotic cells. Rad9, Rad1 and Hus1 deficient cells are hypersensitive to ionizing radiation and mouse cells deleted for anyone of the three genes are highly sensitive to the killing by gamma rays. We propose that ionizing radiation-induced transcription of these genes is a mechanism by which cells respond to radiation-induced damage. In this study we used quantitative real-time RT-PCR(qPCR) to analyze the mRNA levels of Rad9, Rad1 and Hus1 in various tissues isolated from mice that were either mock irradiated or exposed to 10 Gy gamma radiation. Our results indicated that the mRNA levels of Rad9, Rad1 and Hus1 genes were very different among these tissues, and we found high natural levels of mRNA in the spleen, lung, ovary and testis of mice before exposure to radiation. The mRNA levels of the three genes were well correlated across these tissues, being high, medium or low in each of the tissues simultaneously. The mRNA levels of the three genes were analyzed at 2, 6, 12, 24 and 48 h after irradiation. In most tissues Rad9 was strongly induced at 2 and 12 h time points and Hus1 was strongly induced at 2, 12 and 48 h time points, but Rad1 was minimally induced in most of the tissues with the exception of slightly higher levels in the heart and lung tissues at the 48 h time point. These results suggest that the regulation mechanisms for the mRNA levels of the three genes in response to ionizing radiation are complex and not well orchestrated. We also detected the induction of Rad9 and Hus1 proteins in the heart and liver of the animals after irradiation, and found that Rad9 protein levels were highly induced in both the heart and liver, while the Hus1 protein levels were significantly induced only in the liver, suggesting that Rad9 and Hus1 protein levels are not regulated in a coordinated manner in response to irradiation. We then went on to measure the mRNA levels of the three genes and the Rad9 and Hus1 protein levels in the mouse liver cell line (NCTC 1469) in response to irradiation in vitro. All three genes in the cultured cells were minimally induced at mRNA level, obviously different from the highly dynamic induction in liver. Rad9 and Hus1 were significantly induced at the protein level, but the induced Rad9 protein levels were higher than the Hus1 levels. Taken together, the good correlation of the mRNA levels of Rad9, Hus1 and Rad1 genes across different tissues isolated from the animals that were mock irradiated and the lack of correlation in mRNA as well as protein levels after irradiation suggest that the 9-1-1 complex has evolved to play various physiological roles in tissues rather than dealing with high doses of gamma radiation or other genotoxic agents. (C) 2015 by Radiation Research Society

submitted time 2016-05-12 Hits715Downloads424 Comment 0

5. chinaXiv:201605.01410 [pdf]

The Roles of p21(Waf1/CIP1) and Hus1 in Generation and Transmission of Damage Signals Stimulated by Low-Dose Alpha-Particle Irradiation

Zhao, Ye; Wang, Jun; Chen, Shaopeng; Yuan, Hang; Xu, An; Wu, Lijun; Ma, Xiaoyan; Hang, Haiying; Ma, Xiaoyan; Hang, Haiying; Wang, Jun; Chen, Shaopeng; Yuan, Hang; Xu, An; Wu, Lijun; Wu, Lijun
Subjects: Biology >> Biophysics >> Biology

Previously reported studies have demonstrated the involvement of p21(Waf1/CIP1) in radiation-induced bystander effects (RIBE). Mouse embryonic fibroblasts (MEFs) lacking Hus1 fail to proliferate in vitro, but inactivation of p21 allows for the continued growth of Hus1-deficient cells, indicating the close connection between p21 and Hus1 cells. In this study, wildtype MEFs, Hus1(+/+)p21(-/-) MEFs and p21(-/-)Hus1(-/-) MEFs were used in a series of radiation-induced bystander effect experiments, the roles of p21 and Hus1 in the induction and transmission of radiation-induced damage signals were investigated. Our results showed that after 5 cGy alpha particle irradiation, wild-type MEFs induced significant increases in gamma-H2AX foci and micronuclei formation in bystander cells, whereas the bystander effects were not detectable in p21(-/-)Hus1(+/+) MEFs and were restored again in p21(-/-)Hus1(-/-) MEFs. Media transfer experiments showed that p21(-/-)Hus1(+/+) MEFs were deficient in the production bystander signals, but could respond to bystander signals. We further investigated the mitogen-activated protein kinases (MAPKs) that might be involved in the bystander effects. It was found that although knocking out p21 did not affect the expression of connexin43 and its phosphorylation, it did result in inactivation of some MAPK signal pathway kinases, including JNK1/2, ERK1/2 and p38, as well as a decrease in reactive oxygen species (ROS) levels in irradiated cells. However, the activation of MAPK kinases and the ROS levels in irradiated cells were restored in the cell line by knocking out Hus1. These results suggest that p21(Waf1/CIP1) and Hus1 play crucial roles in the generation and transmission of bystander damage signals after low-dose a particle irradiation. (C) 2015 by Radiation Research

submitted time 2016-05-12 Hits642Downloads400 Comment 0

6. chinaXiv:201605.01327 [pdf]

Computational analysis of antigenic epitopes of avian influenza A (H7N9) viruses

Liu Mi; Song TingRui; Hua Sha; Wu AiPing; Jiang TaiJiao; Liu Mi; Hua Sha
Subjects: Biology >> Biophysics >> Biology

Influenza virus can rapidly change its antigenicity, via mutation in the hemagglutinin (HA) protein, to evade host immunity. The emergence of the novel human-infecting avian H7N9 virus in China has caused widespread concern. However, evolution of the antigenicity of this virus is not well understood. Here, we inferred the antigenic epitopes of the HA protein from all H7 viruses, based on the five well-characterized HA epitopes of the human H3N2 virus. By comparing the two major H7 phylogenetic lineages, i.e., the Eurasian lineage and the North American lineage, we found that epitopes A and B are more frequently mutated in the Eurasian lineage, while epitopes B and C are more frequently mutated in the North American lineage. Furthermore, we found that the novel H7N9 virus (derived from the Eurasian lineage) isolated in China in the year 2013, contains six frequently mutated sites on epitopes that include site 135, which is located in the receptor binding domain. This indicates that the novel H7N9 virus that infects human may already have been subjected to gradual immune pressure and receptor-binding variation. Our results not only provide insights into the antigenic evolution of the H7 virus but may also help in the selection of suitable vaccine strains.

submitted time 2016-05-11 Hits732Downloads442 Comment 0

7. chinaXiv:201605.01324 [pdf]

Molecular characteristics and evolutionary analysis of a very virulent infectious bursal disease virus

Li Zan; Zhu Ping; Qi XiaoLe; Ren XianGang; Wang XiaoMei; Cui Lei; Li Zan
Subjects: Biology >> Biophysics >> Biology

Infectious bursal disease virus (IBDV) poses a significant threat to the poultry industry. Viral protein 2 (VP2), the major structural protein of IBDV, has been subjected to frequent mutations that have imparted tremendous genetic diversity to the virus. To determine how amino acid mutations may affect the virulence of IBDV, we built a structural model of VP2 of a very virulent strain of IBDV identified in China, vvIBDV Gx, and performed a molecular dynamics simulation of the interaction between virulence sites. The study showed that the amino acid substitutions that distinguish vvIBDV from attenuated IBDV (H253Q and T284A) favor a hydrophobic and flexible conformation of beta-barrel loops in VP2, which could promote interactions between the virus and potential IBDV-specific receptors. Population sequence analysis revealed that the IBDV strains prevalent in East Asia show a significant signal of positive selection at virulence sites 253 and 284. In addition, a signal of co-evolution between sites 253 and 284 was identified. These results suggest that changes in the virulence of IBDV may result from both the interaction and the co-evolution of multiple amino acid substitutions at virulence sites.

submitted time 2016-05-11 Hits728Downloads402 Comment 0

8. chinaXiv:201605.01312 [pdf]

Recent advance in the structural analysis of HIV-1 envelope protein

Matsuda, Zene
Subjects: Biology >> Biophysics >> Biology

Human immunodeficiency virus type I (HIV-1), a causative agent of AIDS, is affecting today more than 35 millions of people worldwide. The advance of anti-HIV chemotherapy has made AIDS a chronic non-fatal disease in resourceful countries. Long-awaited anti-HIV-1 vaccine is still not with us yet; however, great progress in structural analyses of the envelope protein of HIV-1 in recent years starts to shed light on rational intervention targeted at the envelope protein, as will be reviewed in this article.

submitted time 2016-05-11 Hits632Downloads366 Comment 0

9. chinaXiv:201605.01182 [pdf]

Theoretical study on the bactericidal nature of nanopatterned surfaces

Xue, Fudong; Liu, Junjie; Guo, Longfang; Zhang, Lirong; Li, Qianzhong; Xue, Fudong
Subjects: Biology >> Biophysics >> Biology

A natural biomaterial has been discovered with bactericidal activities, which is mainly attributed to its nanopatterned surface structure. The surface of Clanger cicada (Psaltoda claripennis) wings has been identified as a natural bactericidal material, which has lead to the emergence of research on the development of novel antibacterial surfaces. From the interactions between bacterial biofilms and nanopatterned surface structures, a new mechanical model is proposed that investigates the rupture of bacterial cells within the framework of the "stretching" theory. The effect of surface nanoroughness on the survival of bacterial cells is evaluated by determining the stretching ability of their cell walls. The results, calculated using Gram-positive and Gram-negative bacteria as examples, show a correlation between the stretching of the cell wall and the geometric parameters of the surface structures. The theoretical results indicate that for a given cell rigidity, the bactericidal nature of the surface is determined by the geometric parameters of the surface structures. (C) 2015 Elsevier Ltd. All rights reserved.

submitted time 2016-05-11 Hits993Downloads543 Comment 0

10. chinaXiv:201605.00753 [pdf]

Emerging roles of non-coding RNAs in epigenetic regulation

Chen, Juan; Xue, Yuanchao;
Subjects: Biology >> Biophysics >> Biology

Recent deep sequencing surveys of mammalian genomes have unexpectedly revealed pervasive and complex transcription and identified tens of thousands of RNA transcripts that do not code for proteins. These non-coding RNAs (ncRNAs) highlight the central role of RNA in gene regulation. ncRNAs are arbitrarily divided into two main groups: The first includes small RNAs, such as miRNAs, piRNAs, and endogenous siRNAs, that usually range from 20 to 30 nt, while the second group includes long non-coding RNAs (lncRNAs), which are typically more than 200 nt in length. These ncRNAs were initially thought to merely regulate gene expression at the post-transcriptional level, but recent studies have indicated that ncRNAs, especially lncRNAs, are extensively associated with diverse chromatin remodeling complexes and target them to specific genomic loci to alter DNA methylation or histone status. These findings suggest an emerging theme of ncRNAs in epigenetic regulation. In this review, we discuss the wide spectrum of ncRNAs in the regulation of DNA methylation and chromatin state, as well as the key questions that needs to be investigated and acknowledging the elegant design of these intriguing macromolecules.

submitted time 2016-05-05 Hits825Downloads444 Comment 0

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