Science China. Life sciences (Sci China Life Sci)

Publications in this journal

• Article: Genome-wide identification of cancer-related polyadenylated and non-polyadenylated RNAs in human breast and lung cell lines.

  Guoguang Zhao, Fei Jiao, Qi Liao, Haitao Luo, Hui Li, Liang Sun, Dechao Bu, Kuntao Yu, Yi Zhao, Runsheng Chen
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  ABSTRACT: Eukaryotic mRNAs consist of two forms of transcripts: poly(A)+ and poly(A)-, based on the presence or absence of poly(A) tails at the 3' end. Poly(A)+ mRNAs are mainly protein coding mRNAs, whereas the functions of poly(A)- mRNA are largely unknown. Previous studies have shown that a significant proportion of gene transcripts are poly(A)- or bimorphic (containing both poly(A)+ and poly(A)- transcripts). We compared the expression levels of poly(A)- and poly(A)+ RNA mRNAs in normal and cancer cell lines. We also investigated the potential functions of these RNA transcripts using an integrative workflow to explore poly(A)+ and poly(A)- transcriptome sequences between a normal human mammary gland cell line (HMEC) and a breast cancer cell line (MCF-7), as well as between a normal human lung cell line (NHLF) and a lung cancer cell line (A549). The data showed that normal and cancer cell lines differentially express these two forms of mRNA. Gene ontology (GO) annotation analyses hinted at the functions of these two groups of transcripts and grouped the differentially expressed genes according to the form of their transcript. The data showed that cell cycle-, apoptosis-, and cell death-related functions corresponded to most of the differentially expressed genes in these two forms of transcripts, which were also associated with the cancers. Furthermore, translational elongation and translation functions were also found for the poly(A)- protein-coding genes in cancer cell lines. We demonstrate that poly(A)- transcripts play an important role in cancer development.
  Science China. Life sciences 05/2013;
• Article: Functional evaluation of iodoacetic acid induced photoreceptor degeneration in the cat.

  Yan Nan, Qin Zhang, Chaoran Ren, Xin Huang, Jie Gao, Xiaoxin Li, Mingliang Pu
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  ABSTRACT: Iodoacetic acid (IAA) has been applied to different species to acutely induce photoreceptor degeneration. The purpose of the present study was to use this toxin to thoroughly eliminate photoreceptors and induce complete blindness in the cat. IAA was delivered by single ear vein injection (20 mg·kg(-1)). Six months after the IAA treatment, functional evaluations including pupillary light reflex (PLR), electroretinogram (ERG), visual behavior tests were performed. Morphological examinations were carried out after the functional evaluation. The present result shows that, six months after the IAA application, animals lost visual functions and became completely blind. High dose IAA application via ear vein delivery created an acute and reliable complete photoreceptor degeneration model in the cat. This model can be applied to genetic and cellular therapies for visual function restoration.
  Science China. Life sciences 05/2013;
• Article: A drug from poison: how the therapeutic effect of arsenic trioxide (ATO) on acute promyelocytic leukemia (APL) was discovered.

  Yi Rao, Runhong Li, Daqing Zhang
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  ABSTRACT: It is surprising that, while arsenic trioxide (ATO) is now considered as "the single most active agent in patients with acute promyelocytic leukemia (APL)", the most important discoverer remains obscure and his original papers have not been cited by a single English paper. The discovery was made during the Cultural Revolution when most Chinese scientists and doctors struggled to survive. Beginning with recipes from a countryside practitioner that were vague in applicable diseases, Zhang TingDong and colleagues proposed in the 1970s that a single chemical in the recipe is most effective and that its target is APL. More than 20 years of work by Zhang and colleagues eliminated the confusions about whether and how ATO can be used effectively. Other researchers, first in China and then in the West, followed his lead. Retrospective analysis of data from his own group proved that APL was indeed the most sensitive target. Removal of a trace amount of mercury chloride from the recipe by another group in his hospital proved that only ATO was required. Publication of Western replication in 1998 made the therapy widely accepted, though neither Western, nor Chinese authors of English papers on ATO cited Zhang's papers in the 1970s. This article focuses on the early papers of Zhang, but also suggests it worth further work to validate Chinese reports of ATO treatment of other cancers, and infers that some findings published in Chinese journals are of considerable value to patients and that doctors from other countries can benefit from the clinical experience of Chinese doctors with the largest population of patients.
  Science China. Life sciences 05/2013;
• Article: Immunogenicity analysis following human immunodeficiency virus recombinant DNA and recombinant vaccinia virus Tian Tan prime-boost immunization.

  Cunxia Liu, Shouwen Du, Chang Li, Yuhang Wang, Maopeng Wang, Yi Li, Ronglan Yin, Xiao Li, Dayong Ren, Yanqing Qin, Jingqiang Ren, Ningyi Jin
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  ABSTRACT: This study assessed and compared the immunogenicity of various immunization strategies in mice using combinations of recombinant DNA (pCCMp24) and recombinant attenuated vaccinia virus Tian Tan (rddVTT-CCMp24). Intramuscular immunization was performed on days 0 (prime) and 21 (boost). The immunogenicity of the vaccine schedules was determined by measuring human immunodeficiency virus (HIV)-specific binding antibody levels and cytokine (interleukin-2 and interleukin-4) concentrations in peripheral blood, analyzing lymphocyte proliferation capacity against HIV epitopes and CD4(+)/CD8(+) cell ratio, and monitoring interferon-gamma levels at different times post-immunization. The results showed that pCCMp24, rddVTT-CCMp24 and their prime-boost immunization induced humoral and cellular immune responses. The pCCMp24/rddVTT-CCMp24 immunization strategy increased CD8(+) T cells and induced more IFN-γ-secreting cells compared with single-shot rDNA. The prime-boost immunization strategy also induced the generation of cellular immunological memory to HIV epitope peptides. These results demonstrated that prime-boost immunization with rDNA and rddVTT-CCMp24 had a tendency to induce greater cellular immune response than single-shot vaccinations, especially IFN-γ response, providing a basis for further studies.
  Science China. Life sciences 05/2013;
• Article: Mitochondrial genome sequences of Artemia tibetiana and Artemia urmiana: assessing molecular changes for high plateau adaptation.

  Hangxiao Zhang, Qibin Luo, Jing Sun, Fei Liu, Gang Wu, Jun Yu, Weiwei Wang
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  ABSTRACT: Brine shrimps, Artemia (Crustacea, Anostraca), inhabit hypersaline environments and have a broad geographical distribution from sea level to high plateaus. Artemia therefore possess significant genetic diversity, which gives them their outstanding adaptability. To understand this remarkable plasticity, we sequenced the mitochondrial genomes of two Artemia tibetiana isolates from the Tibetan Plateau in China and one Artemia urmiana isolate from Lake Urmia in Iran and compared them with the genome of a low-altitude Artemia, A. franciscana. We compared the ratio of the rate of nonsynonymous (Ka) and synonymous (Ks) substitutions (Ka/Ks ratio) in the mitochondrial protein-coding gene sequences and found that atp8 had the highest Ka/Ks ratios in comparisons of A. franciscana with either A. tibetiana or A. urmiana and that atp6 had the highest Ka/Ks ratio between A. tibetiana and A. urmiana. Atp6 may have experienced strong selective pressure for high-altitude adaptation because although A. tibetiana and A. urmiana are closely related they live at different altitudes. We identified two extended termination-associated sequences and three conserved sequence blocks in the D-loop region of the mitochondrial genomes. We propose that sequence variations in the D-loop region and in the subunits of the respiratory chain complexes independently or collectively contribute to the adaptation of Artemia to different altitudes.
  Science China. Life sciences 05/2013; 56(5):440-52.
• Article: Protein array of Coxiella burnetii probed with Q fever sera.

  Xile Wang, Xiaolu Xiong, Stephen Graves, John Stenos, Bohai Wen
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  ABSTRACT: Coxiella burnetii is the etiological agent of Q fever. To identify its major seroreactive proteins, a subgenomic protein array was developed. A total of 101 assumed virulence-associated recombinant proteins of C. burnetii were probed with sera from mice experimentally infected with C. burnetii and sera from Q fever patients. Sixteen proteins were recognized as major seroreactive antigens by the mouse sera. Seven of these 16 proteins reacted positively with at least 45% of Q fever patient sera. Notably, HspB had the highest fluorescence intensity value and positive frequency of all the proteins on the array when probed with both Q fever patient sera and mouse sera. These results suggest that these seven major seroreactive proteins, particularly HspB, are potential serodiagnostic and subunit vaccine antigens of Q fever.
  Science China. Life sciences 05/2013; 56(5):453-9.
• Article: Immunosenescence and age-related viral diseases.

  Yongchao Ma, Min Fang
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  ABSTRACT: Immunosenescence is described as a decline in the normal functioning of the immune system associated with physiologic ageing. Immunosenescence contributes to reduced efficacy to vaccination and increased susceptibility to infectious diseases in the elderly. Extensive studies of laboratory animal models of ageing or donor lymphocyte analysis have identified changes in immunity caused by the ageing process. Most of these studies have identified phenotypic and functional changes in innate and adaptive immunity. However, it is unclear which of these defects are critical for impaired immune defense against infection. This review describes the changes that occur in innate and adaptive immunity with ageing and some age-related viral diseases where defects in a key component of immunity contribute to the high mortality rate in mouse models of ageing.
  Science China. Life sciences 05/2013; 56(5):399-405.
• Article: Different quasispecies with great mutations hide in the same subgroup J field strain of avian leukosis virus.

  Yaqing Mao, Weihua Li, Xuan Dong, Jinhua Liu, Peng Zhao
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  ABSTRACT: Blood samples were collected from a local strain of chickens associated with serious tumor cases in Shandong Province. The samples were inoculated into chicken embryo fibroblast and DF-1 cells for virus isolation and identification, respectively. The inoculated cells were screened for three common chicken tumor viruses. Nine strains of avian leukosis virus subgroup J (ALV-J) were identified, and were designated LY1201-LY1209. The env gene from the LY1201 strain was amplified and cloned. All nine resultant env clones (clones 01-09) were sequenced, and the gp85 and gp37 amino acid regions were subjected to homology analysis. Clones 01 and 03 had 10 amino acid deletions in the gp85 region compared to the other seven clones, suggesting that at least two quasispecies with obvious mutations coexist in the same field strain. Among these nine clones, three had identical gp85 and gp37 sequences, and were recognized as the dominant LY1201 quasispecies. The amino acid sequence homology of gp37 and gp85 among the nine clones was 98.5%-100.0% and 96.6%-100.0% respectively, suggesting that the gp85 region of the env gene can better display the quasispecies diversity of ALV-J than gp37.
  Science China. Life sciences 05/2013; 56(5):414-20.
• Article: Immune selection, senescence and adjuvant.

  Hong Tang
  Science China. Life sciences 05/2013; 56(5):391.
• Article: miRNA-711-SP1-collagen-I pathway is involved in the anti-fibrotic effect of pioglitazone in myocardial infarction.

  Na Zhao, Haiyi Yu, Haitao Yu, Min Sun, Youyi Zhang, Ming Xu, Wei Gao
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  ABSTRACT: Although microRNAs (miRNAs) have been intensively studied in cardiac fibrosis, their roles in drug-mediated anti-fibrotic therapy are still unknown. Previously, Pioglitazone attenuated cardiac fibrosis and increased miR-711 experimentally. We aimed to explore the role and mechanism of miR-711 in pioglitazone-treated myocardial infarction in rats. Our results showed that pioglitazone significantly reduced collagen-I levels and increased miR-711 expression in myocardial infarction heart. Pioglitazone increased the expression of miR-711 in cardiac fibroblasts, and overexpression of miR-711 suppressed collagen-I levels in angiotensin II (Ang II)-treated or untreated cells. Transfection with antagomir-711 correspondingly abolished the pioglitazone-induced reduction in collagen-I levels. Bioinformatics analysis identified SP1, which directly promotes collagen-I synthesis, as the putative target of miR-711. This was confirmed by luciferase assay and western blot analysis. Additionally, increased SP1 expression was attenuated by pioglitazone in myocardial infarction heart. Furthermore, transfection of antagomir-711 attenuated pioglitazone-reduced SP1 expression in cardiac fibroblasts with or without Ang II stimulation. We conclude that pioglitazone up-regulated miR-711 to reduce collagen-I levels in rats with myocardial infarction. The miR-711-SP1-collagen-I pathway may be involved in the anti-fibrotic effects of pioglitazone. Our findings may provide new strategies for miRNA-based anti-fibrotic drug research.
  Science China. Life sciences 05/2013; 56(5):431-9.
• Article: Medullary thymic epithelial cells, the indispensable player in central tolerance.

  Yaoyao Shi, Mingzhao Zhu
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  ABSTRACT: Crosstalk between thymocytes and thymic epithelial cells is critical for T cell development and the establishment of central tolerance. Medullary thymic epithelial cells (mTECs) play important roles in the late stage of T cell development, especially negative selection and Treg generation. The function of mTECs is highly dependent on their characteristic features such as ectopic expression of peripheral tissue restricted antigens (TRAs) and their master regulator-autoimmune regulator (Aire), expression of various chemokines and cytokines. In this review, we summarize the current understanding of cellular and molecular mechanisms of mTEC development and its functions in T cell development and the establishment of central tolerance. The open questions in this field are also discussed. Understanding the function and underlying mechanisms of mTECs will contribute to the better control of autoimmune diseases and the improvement of immune reconstitution during aging or after infection, chemotherapy or radiotherapy.
  Science China. Life sciences 05/2013; 56(5):392-8.
• Article: pyrG is required for maintaining stable cellular uracil level and normal sporulation pattern under excess uracil stress in Aspergillus nidulans.

  Xianyun Sun, Jufen Zhu, Li Bao, Chengcheng Hu, Cheng Jin, Steven D Harris, Hongwei Liu, Shaojie Li
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  ABSTRACT: Tight control of the intracellular uracil level is believed to be important to reduce the occurrence of uracil incorporation into DNA. The pyrG gene of Aspergillus nidulans encodes orotidine 5'-phosphate decarboxylase, which catalyzes the conversion of orotidine monophosphate (OMP) to uridine monophosphate (UMP). In this study, we found that pyrG is critical for maintaining uracil at a low concentration in A. nidulans cells in the presence of exogenous uracil. Excess uracil and its derivatives had a stronger inhibitory effect on the growth of the pyrG89 mutant with defective OMP decarboxylase activity than on the growth of wild type, and induced sexual development in the pyrG89 mutant but not in wild type. Analysis of transcriptomic responses to excess uracil by digital gene expression profiling (DGE) revealed that genes related to sexual development were transcriptionally activated in the pyrG89 mutant but not in wild type. Quantitative analysis by HPLC showed that the cellular uracil level was 6.5 times higher in the pyrG89 mutant than in wild type in the presence of exogenous uracil. This study not only provides new information on uracil recycling and adaptation to excess uracil but also reveals the potential effects of OMP decarboxylase on fungal growth and development.
  Science China. Life sciences 05/2013; 56(5):467-75.
• Article: Electron microscopy: essentials for viral structure, morphogenesis and rapid diagnosis.

  Ying Zhang, Tao Hung, Jingdong Song, Jinsheng He
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  ABSTRACT: Electron microscopy (EM) should be used in the front line for detection of agents in emergencies and bioterrorism, on accounts of its speed and accuracy. However, the number of EM diagnostic laboratories has decreased considerably and an increasing number of people encounter difficulties with EM results. Therefore, the research on viral structure and morphologyant in EM diagnostic practice. EM has several technological advantages, and should be a fundamental tool in clinical diagnosis of viruses, particularly when agents are unknown or unsuspected. In this article, we review the historical contribution of EM to virology, and its use in virus differentiation, localization of specific virus antigens, virus-cell interaction, and viral morphogenesis. It is essential that EM investigations are based on clinical and comprehensive pathogenesis data from light or confocal microscopy. Furthermore, avoidance of artifacts or false results is necessary to exploit fully the advantages while minimizing its limitations.
  Science China. Life sciences 05/2013; 56(5):421-30.
• Article: Habitat suitability modeling of amphibian species in southern and central China: environmental correlates and potential richness mapping.

  Youhua Chen
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  ABSTRACT: Successful wildlife management must take into account suitable habitat areas. Information on the correlation between distribution ranges and environmental conditions would, therefore, improve the efficacy of in-situ conservation of wildlife. In this contribution, correlations between environmental factors and the distribution of 51 amphibians in southern and central China were investigated. Ecological niche factor analysis (ENFA) at a spatial resolution of 1° latitude×1° longitude identified a mixture of climatic and habitat factors as important predictors of the occurrence of individual species. The aims of the present work were (i) to evaluate potential distributions of amphibians based on the suitability of areas; (ii) to identify the major environmental descriptors upon which they depend; and (iii) to identify areas of potential high richness that have been overlooked in available inventories. Most of the predicted species ranges of species covered the majority of southern and central China. Six richness hotspots were predicted, of which four have been described previously, but two overlooked (SE Fujian and SE Qinghai). The prediction model was considered to be relatively accurate and it is recommended that these two new potential hotspots should be subjected to further evaluation and sampling efforts. Amphibians have high ecological preference for high humidity and precipitation, and low annual frost days. ENFA is a useful tool in wildlife conservation assessment because it is able to identify potential hotspots where studies on the correlations between environmental descriptors and the occurrence of particular species could be focused.
  Science China. Life sciences 05/2013; 56(5):476-84.
• Article: Physical characteristics of Chinese Hakka.

  Lianbin Zheng, Yonglan Li, Shunhua Lu, Jinping Bao, Yang Wang, Xiaorui Zhang, Hong Xue, Wenguo Rong
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  ABSTRACT: Using standard and internationally validated methods, 86 anthropologic characteristics were determined in 650 male (305 from urban areas and 345 from rural areas) and 704 female (331 from urban areas, 373 from rural areas) Chinese Hakka adults living in Guangdong and Jiangxi. The data were used to calculate 24 anthropologic indices, which were analyzed statistically. The physical characteristics of Hakka subjects were analyzed and compared with reference ethnic data. There were four main findings of this study. First, a small proportion of Hakka adults had an eye fold on the upper eyelid, but a large proportion had a mongoloid fold. The eye slits were narrow in most adults, had a medium nasal root height and straight bridges, and most of the external angles were prominent. The nasal base was upturned in most men. The distributions of the three types of nasal base in women were similar. The proportions of subjects with middle and high alae nasi heights were high and similar. Males with a maximum nostril diameter were mostly classified as transverse and oblique, while many women were classified as transverse and had relatively wide alae nasi. The round lobe type was the most common. Upper lip skin height was mostly classified as medium. Lips were classified as thin. The hair was black, eyes were brown, and the skin was yellowish. Second, the head length was long in male Hakka. The minimum frontal breadth, face breadth, lip height, and interocular breadth were similar to those of North-Asian populations. Meanwhile, head breadth, morphological facial height, nose breadth, mouth breadth, and nose height were similar to those of South-Asian populations. Head length was long in female Hakka. The minimum frontal breadth, face breadth, lip height, and interocular breadth were similar to those of North-Asian populations. Head breadth, nose breadth, and mouth breadth were similar to those of South-Asian populations. Third, the stature of male and female Hakka in urban and rural areas was classified as medium. The proportions of male and female Hakka classified as mesocephaly (length-breadth index of the head), hypsicephalic type, metriocephalic type (breadth-height index of the head) mesorrhiny, long trunk, subbrachyskelic type, broad shoulder breadth, and narrow distance between iliac crests were higher than those of other types. Finally, principal component analyses showed that the physical characteristics of Hakka were between those of South-Asian and North-Asian ethnic populations, but were generally closer to those of North-Asian populations in China.
  Science China. Life sciences 04/2013;
• Article: pORF5 plasmid protein of Chlamydia trachomatis induces MAPK-mediated pro-inflammatory cytokines via TLR2 activation in THP-1 cells.

  Hui Zhou, Qiulin Huang, Zhongyu Li, Yimou Wu, Xiaobing Xie, Kangkang Ma, Wenjuan Cao, Zhou Zhou, Chunxue Lu, Guangming Zhong
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  ABSTRACT: Infection with Chlamydia trachomatis induces inflammatory pathologies in the urogenital tract that can lead to infertility and ectopic pregnancy. Pathogenesis of infection has been mostly attributed to excessive cytokine production. However, precise mechanisms on how C. trachomatis triggers this production, and which protein(s) stimulate inflammatory cytokines remains unknown. In the present study, the C. trachomatis pORF5 protein induced tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-8 (IL-8) in dose- and time-dependent manners in the THP-1 human monocyte cell line. We found that intracellular p38/mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)/MAPK signaling pathways were required for the induction of TNF-α, IL-1β and IL-8. Blockade of toll-like receptor 2 (TLR2) signaling reduced induction levels of TNF-α, IL-8 and IL-1β. We concluded that the C. trachomatis pORF5 protein might contribute to the inflammatory processes associated with chlamydial infections.
  Science China. Life sciences 04/2013;
• Article: A Zernike-moment-based non-local denoising filter for cryo-EM images.

  Jia Wang, Changcheng Yin
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  ABSTRACT: Cryo-electron microscopy (cryo-EM) plays an important role in determining the structure of proteins, viruses, and even the whole cell. It can capture dynamic structural changes of large protein complexes, which other methods such as X-ray crystallography and nuclear magnetic resonance analysis find difficult. The signal-to-noise ratio of cryo-EM images is low and the contrast is very weak, and therefore, the images are very noisy and require filtering. In this paper, a filtering method based on non-local means and Zernike moments is proposed. The method takes into account the rotational symmetry of some biological molecules to enhance the signal-to-noise ratio of cryo-EM images. The method may be useful in cryo-EM image processing such as the automatic selection of particles, orientation determination, and the building of initial models.
  Science China. Life sciences 04/2013; 56(4):384-90.
• Article: Research status and prospect of stem cells in the treatment of diabetes mellitus.

  Xiaofang Liu, Yunfang Wang, Yali Li, Xuetao Pei
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  ABSTRACT: Beta cell mass and function are decreased to varying degrees in diabetes. Islet cell replacement or regenerative therapy may offer great therapeutic promise to people with diabetes. In addition to primary pancreatic β cells, recent studies on regeneration of functional insulin producing cells (IPCs) revealed that several alternative cell sources, including embryonic stem cells, induced pluripotent stem cells and adult stem cells, can generate IPCs by differentiation, reprogramming, and trans-differentiation. In this review, we discuss stem cells as a potential alternative cell source for the treatment of diabetes.
  Science China. Life sciences 04/2013; 56(4):306-12.