Anlong Xu

Publications (121)453.61 Total impact

• Article: Genome-Wide Analyses of Amphioxus MicroRNAs Reveal an Immune Regulation via miR-92d Targeting C3.

  Rirong Yang, Tingting Zheng, Xingsheng Cai, Yingcai Yu, Cuiling Yu, Lei Guo, Shengfeng Huang, Wei Zhu, Ruimin Zhu, Qingyu Yan, Zhenghua Ren, Shangwu Chen, Anlong Xu
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  ABSTRACT: Recently, amphioxus has served as a model for studying the origin and evolution of vertebrate immunity. However, little is known about how microRNAs (miRNAs) are involved in the immune defense in amphioxus. In this article, we present a systematic study of amphioxus miRNAs in the acute-phase response to bacterial infection; miR-92d was found to regulate the complement pathway in this basal chordate. We identified all 155 possible miRNAs present in the amphioxus Branchiostoma belcheri genome by bioinformatics analyses, including 57 newly identified miRNAs (called bbe-miRNAs), and characterized the miRNA expression pattern. Four miRNAs (bbe-miR-7, bbe-miR-4868a, bbe-miR-2065, and bbe-miR-34b) were upregulated and bbe-miR-92d was downregulated under the challenge of both Vibrio anguillarum and Staphylococcus aureus bacteria. We further predicted miRNA targets and identified mRNA targets of immune-related miRNA using the hybrid PCR method. We propose that miR-92d regulates the complement pathway through targeting C3 for controlling the acute immune response to bacterial infections. This study provides evidence for the complex immune regulation of miRNAs in the acute-phase response in basal chordates.
  The Journal of Immunology 01/2013; · 5.79 Impact Factor
• Article: Genome-wide alternative polyadenylation in animals: insights from high-throughput technologies.

  Yu Sun, Yonggui Fu, Yuxin Li, Anlong Xu
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  ABSTRACT: Alternative polyadenylation (APA) plays an important role in gene expression by affecting mRNA stability, translation, and translocation in cells. However, genome-wide APA events have only recently been subjected to more systematic analysis with newly developed high-throughput methods. In this review, we focus on the recent technological development of APA analyses on a genome-wide scale, as well as the impact of APA switches on a number of critical biological processes in animals, including cell proliferation, differentiation, and oncogenic transformation. With the highly enlarged scope of genome-wide APA analyses, the APA regulations of various biological processes have increasingly become a new paradigm for the regulation of gene transcription and translation.
  Journal of Molecular Cell Biology 10/2012;
• Article: Dynamic landscape of tandem 3' UTRs during zebrafish development.

  Yuxin Li, Yu Sun, Yonggui Fu, Mengzhen Li, Guangrui Huang, Chenxu Zhang, Jiahui Liang, Shengfeng Huang, Gaoyang Shen, Shaochun Yuan, Liangfu Chen, Shangwu Chen, Anlong Xu
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  ABSTRACT: Tandem 3' untranslated regions (UTRs), produced by alternative polyadenylation (APA) in the terminal exon of a gene, could have critical roles in regulating gene networks. Here we profiled tandem poly(A) events on a genome-wide scale during the embryonic development of zebrafish (Danio rerio) using a recently developed SAPAS method. We showed that 43% of the expressed protein-coding genes have tandem 3' UTRs. The average 3' UTR length follows a V-shaped dynamic pattern during early embryogenesis, in which the 3' UTRs are first shortened at zygotic genome activation, and then quickly lengthened during gastrulation. Over 4000 genes are found to switch tandem APA sites, and the distinct functional roles of these genes are indicated by Gene Ontology analysis. Three families of cis-elements, including miR-430 seed, U-rich element, and canonical poly(A) signal, are enriched in 3' UTR-shortened/lengthened genes in a stage-specific manner, suggesting temporal regulation coordinated by APA and trans-acting factors. Our results highlight the regulatory role of tandem 3' UTR control in early embryogenesis and suggest that APA may represent a new epigenetic paradigm of physiological regulations.
  Genome Research 09/2012; 22(10):1899-906. · 13.61 Impact Factor
• Article: HaploMerger: reconstructing allelic relationships for polymorphic diploid genome assemblies.

  Shengfeng Huang, Zelin Chen, Guangrui Huang, Ting Yu, Ping Yang, Jie Li, Yonggui Fu, Shaochun Yuan, Shangwu Chen, Anlong Xu
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  ABSTRACT: Whole-genome shotgun assembly has been a long-standing issue for highly polymorphic genomes, and the advent of next-generation sequencing technologies has made the issue more challenging than ever. Here we present an automated pipeline, HaploMerger, for reconstructing allelic relationships in a diploid assembly. HaploMerger combines a LASTZ-ChainNet alignment approach with a novel graph-based structure, which helps to untangle allelic relationships between two haplotypes and guides the subsequent creation of reference haploid assemblies. The pipeline provides flexible parameters and schemes to improve the contiguity, continuity, and completeness of the reference assemblies. We show that HaploMerger produces efficient and accurate results in simulations and has advantages over manual curation when applied to real polymorphic assemblies (e.g., 4%-5% heterozygosity). We also used HaploMerger to analyze the diploid assembly of a single Chinese amphioxus (Branchiostoma belcheri) and compared the resulting haploid assemblies with EST sequences, which revealed that the two haplotypes are not only divergent but also highly complementary to each other. Taken together, we have demonstrated that HaploMerger is an effective tool for analyzing and exploiting polymorphic genome assemblies.
  Genome Research 05/2012; 22(8):1581-8. · 13.61 Impact Factor
• Article: Comparative Immune Systems in Animals

  Shaochun Yuan, Xin Tao, Shengfeng Huang, Shangwu Chen, Anlong Xu
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  ABSTRACT: Animal immune systems can be classified into those of innate and adaptive immunity. It is generally thought that the former is universal for all animals and depends on germ line–encoded receptors that recognize highly conserved pathogen-associated molecular patterns (PAMPs), whereas the latter is vertebrate specific and mediated primarily by lymphocytes bearing a unique antigen receptor. However, novel adaptive or adaptive-like immunities have been found in invertebrates and jawless vertebrates, and extraordinarily complex innate immunities, created through huge expansions of many innate gene families, have been found in cephalochordate amphioxus and echinoderm sea urchin recently. These studies not only promote immunologists to seek novel immune mechanisms in species evolutionarily below vertebrates but also raise questions about the origin and evolution of vertebrate immunities. Therefore, we summarize studies from the past decade on comparative immunology in several transition species to help understan...
  04/2012;
• Article: More single-nucleotide mutations surround small insertions than small deletions in primates.

  Shengfeng Huang, Ting Yu, Zelin Chen, Shaochun Yuan, Shangwu Chen, Anlong Xu
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  ABSTRACT: Early studies have shown that single-nucleotide mutation rates increase close to insertions and deletions, but it is not fully understood how natural selection shapes genome-wide patterns of indels and their nearby single-nucleotide mutations. In this study, we find that, in primates, more single-nucleotide mutations surround small insertions than small deletions. This pattern affects <150 base pair (bp) sequences close to indels and persists under different genomic properties, such as exon/intron/intergenic contexts, repeated/nonrepeated sequences, replication timing, recombination rates, indel density, and guanine-cytosine (GC) content. We propose two different, but not mutually exclusive, hypothetical mechanisms to explain the pattern. One mechanism is that the sequence context preferring insertion formation may also favor nucleotide substitutions. Another mechanism is related to a hypothesis in which indel heterozygosity tends to increase nearby nucleotide substitution rates. It means that if insertions spend more time in heterozygotes, insertions may accumulate more surrounding single-nucleotide changes. In conclusion, we characterize a special genome-wide evolutionary pattern for indels and nearby single-nucleotide changes. This pattern may be driven by natural selection and bias primates' genome evolution and phenotypic variations.
  Human Mutation 03/2012; 33(7):1099-106. · 5.69 Impact Factor
• Article: Identification, synthesis and characterization of a novel antimicrobial peptide HKPLP derived from Hippocampus kuda Bleeker.

  Dandan Sun, Songqing Wu, Chenfeng Jing, Ning Zhang, Dong Liang, Anlong Xu
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  ABSTRACT: A novel gene encoding 55 amino-acid residues has been identified from the brooding pouch cDNA library of Hippocampus kuda Bleeker. The deduced amino-acid sequence is highly homologous to several pleurocidin-like peptides from the winter flounder and comprises a signal peptide, a pro-peptide and a mature peptide. The glycine-rich mature peptide, designated HKPLP, contains 24 amino-acid residues and has been synthesized by solid-phase peptide synthesis. The purified HKPLP exhibits antimicrobial activity against several Gram-positive and Gram-negative bacterial strains at low concentrations (MIC 1.5-7.5 μM). Thermal stability assay data show good heat stability. CD spectroscopy experiments indicate that the dominant contents are anti-parallel and parallel sheets, which may have β-sheet or β-strand motif. It is inferred that HKPLP participates in the host defense during egg fertilization and embryo development as an antimicrobial peptide in brooding pouch.
  The Journal of Antibiotics 01/2012; 65(3):117-121. · 1.65 Impact Factor
• Article: A Global Analysis of Tandem 3'UTRs in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps.

  Peng Tian, Yu Sun, Yuxin Li, Xiang Liu, Liang Wan, Jie Li, Yun Ma, Anlong Xu, Yonggui Fu, Hua Zou
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  ABSTRACT: Alternative polyadenylation (APA) is emerging as a widespread mechanism of gene regulation. The usage of APA sites allows a single gene to encode multiple mRNA transcripts with different 3'-untranslated region (3'UTR) lengths. Many disease processes reflect the importance of the regulation of APA site switching. The objective of this study was to explore the profiling of tandem APA sites in nasal polyps compared with nasal uncinate process mucosa. Sequencing of APA sites (SAPAS) based on second-generation sequencing technology was undertaken to investigate the use of tandem APA sites and identify gene expression patterns in samples from the nasal polyps and nasal uncinate process mucosa of two patients with chronic rhinosinusitis with nasal polyps. The findings of the SAPAS analysis were validated via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). First, the results showed a switching of 3'UTR lengths in nasal polyps compared with nasal uncinate process mucosa. From the two patients, 105 genes that were detected in both patients in the nasal polyps were switched to distal poly(A) sites, and 90 such genes were switched to proximal poly(A) sites. Several Gene Ontology terms were enriched in the list of genes with switched APA sites, including transcription regulation, cell cycle, apoptosis, and metabolism. Second, we detected genes that showed differential expression with at least a 3-fold difference between nasal polyp tissue and nasal uncinate process mucosa. Between the two sample types, 627 genes exhibited differential expression. The qRT-PCR results confirmed our SAPAS results. APA site-switching events of 3'UTRs are prevalent in nasal polyp tissue, and the regulation of gene expression mediated by APA may play an important role in the formation and persistence of nasal polyps. Our results may provide new insights into the possible pathophysiologic processes involved in nasal polyps.
  PLoS ONE 01/2012; 7(11):e48997. · 4.09 Impact Factor
• Article: HTS-PEG: A Method for High Throughput Sequencing of the Paired-Ends of Genomic Libraries.

  Sisi Zhou, Yonggui Fu, Jie Li, Lingyu He, Xingsheng Cai, Qingyu Yan, Xingqiang Rao, Shengfeng Huang, Guang Li, Yiquan Wang, Anlong Xu
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  ABSTRACT: Second generation sequencing has been widely used to sequence whole genomes. Though various paired-end sequencing methods have been developed to construct the long scaffold from contigs derived from shotgun sequencing, the classical paired-end sequencing of the Bacteria Artificial Chromosome (BAC) or fosmid libraries by the Sanger method still plays an important role in genome assembly. However, sequencing libraries with the Sanger method is expensive and time-consuming. Here we report a new strategy to sequence the paired-ends of genomic libraries with parallel pyrosequencing, using a Chinese amphioxus (Branchiostoma belcheri) BAC library as an example. In total, approximately 12,670 non-redundant paired-end sequences were generated. Mapping them to the primary scaffolds of Chinese amphioxus, we obtained 413 ultra-scaffolds from 1,182 primary scaffolds, and the N50 scaffold length was increased approximately 55 kb, which is about a 10% improvement. We provide a universal and cost-effective method for sequencing the ultra-long paired-ends of genomic libraries. This method can be very easily implemented in other second generation sequencing platforms.
  PLoS ONE 01/2012; 7(12):e52257. · 4.09 Impact Factor
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  Available from: PubMed Central

  Article: The conservation and uniqueness of the caspase family in the basal chordate, amphioxus.

  Liqun Xu, Shaochun Yuan, Jun Li, Jie Ruan, Shengfeng Huang, Manyi Yang, Huiqing Huang, Shangwu Chen, Zhenghua Ren, Anlong Xu
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  ABSTRACT: The caspase family, which plays a central role in apoptosis in metazoans, has undergone an expansion in amphioxus, increasing to 45 members through domain recombination and shuffling. In order to shed light on the conservation and uniqueness of this family in amphioxus, we cloned three representative caspase genes, designated as bbtCaspase-8, bbtCaspase-1/2 and bbtCaspase3-like, from the amphioxus Branchiostoma belcheri tsingtauense. We found that bbtCaspase-8 with conserved protein architecture is involved in the Fas-associated death domain-Caspase-8 mediated pro-apoptotic extrinsic pathway, while bbtCaspase3-like may mediate a nuclear apoptotic pathway in amphioxus. Also, bbtCaspase-1/2 can co-localize with bbtFADD2 in the nucleus, and be recruited to the cytoplasm by amphioxus apoptosis associated speck-like proteins containing a caspase recruitment domain, indicating that bbtCaspase-1/2 may serve as a switch between apoptosis and caspase-dependent innate immune response in invertebrates. Finally, amphioxus extrinsic apoptotic pathway related caspases played important roles in early embryogenesis. Our study not only demonstrates the conservation of bbtCaspase-8 in apoptosis, but also reveals the unique features of several amphioxus caspases with novel domain architectures arose some 500 million years ago.
  BMC Biology 09/2011; 9:60. · 5.75 Impact Factor
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  Available from: sysu.edu.cn

  Article: Characterization of bbtTICAM from amphioxus suggests the emergence of a MyD88-independent pathway in basal chordates.

  Manyi Yang, Shaochun Yuan, Shengfeng Huang, Jun Li, Liqun Xu, Huiqing Huang, Xin Tao, Jian Peng, Anlong Xu
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  ABSTRACT: The MyD88-independent pathway, one of the two crucial TLR signaling routes, is thought to be a vertebrate innovation. However, a novel Toll/interleukin-1 receptor (TIR) adaptor, designated bbtTICAM, which was identified in the basal chordate amphioxus, links this pathway to invertebrates. The protein architecture of bbtTICAM is similar to that of vertebrate TICAM1 (TIR-containing adaptor molecule-1, also known as TRIF), while phylogenetic analysis based on the TIR domain indicated that bbtTICAM is the oldest ortholog of vertebrate TICAM1 and TICAM2 (TIR-containing adaptor molecule-2, also known as TRAM). Similar to human TICAM1, bbtTICAM activates NF-κB in a MyD88-independent manner by interacting with receptor interacting protein (RIP) via its RHIM motif. Such activation requires bbtTICAM to form homodimers in endosomes, and it may be negatively regulated by amphioxus SARM (sterile α and armadillo motif-containing protein) and TRAF2. However, bbtTICAM did not induce the production of type I interferon. Thus, our study not only presents the ancestral features of vertebrate TICAM1 and TICAM2, but also reveals the evolutionary origin of the MyD88-independent pathway from basal chordates, which will aid in understanding the development of the vertebrate TLR network.
  Cell Research 09/2011; 21(10):1410-23. · 8.19 Impact Factor
• Article: Synthesis, structures, cellular uptake and apoptosis-inducing properties of highly cytotoxic ruthenium-Norharman complexes.

  Caiping Tan, Shouhai Wu, Sensen Lai, Minxu Wang, Yu Chen, Lingjun Zhou, Yiping Zhu, Wu Lian, Wenlie Peng, Liangnian Ji, Anlong Xu
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  ABSTRACT: Three novel Ru(II) complexes of the general formula [Ru(N-N)(2)(Norharman)(2)](SO(3)CF(3))(2), where N-N = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), 4,7-diphenyl-1,10-phenanthroline (DIP, 3) and Norharman (9H-pyrido[3,4-b]indole) is a naturally occurring β-carboline alkaloid, have been synthesized and characterized. The molecular structures of 1 and 2 have been determined by X-ray diffraction analysis. The cellular uptake efficiencies, in vitro cytotoxicities and apoptosis-inducing properties of these complexes have been extensively explored. Notably, 1-3 exhibit potent antiproliferative activities against a panel of human cancer cell lines with IC(50) values lower than those of cisplatin. Further studies show that 1-3 can cause cell cycle arrest in the G0/G1 phase and induce apoptosis through mitochondrial dysfunction and reactive oxygen species (ROS) generation. In vitro DNA binding studies have also been conducted to provide information about the possible mechanism of action.
  Dalton Transactions 09/2011; 40(34):8611-21. · 3.84 Impact Factor
• Article: Functional conservation and innovation of amphioxus RIP1-mediated signaling in cell fate determination.

  Jun Li, Shaochun Yuan, Lin Qi, Shengfeng Huang, Guangrui Huang, Manyi Yang, Liqun Xu, Yuxin Li, Renwei Zhang, Yingcai Yu, Shangwu Chen, Anlong Xu
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  ABSTRACT: Recently, receptor interacting protein (RIP)-1 has been recognized as an intracellular sensor at the crossroads of apoptosis, necroptosis, and cell survival. To reveal when this crucial molecule originated and how its function in integrating stress signals evolved, in this study we report on two RIP1 homologs in Chinese amphioxus (Branchiostoma belcheri tsingtauense), designated B. belcheri tsingtauense RIP1a and B. belcheri tsingtauense RIP1b. Phylogenetic analysis indicates that they are generated by domain recombination and lineage-specific duplication. Similar to human RIP1, both B. belcheri tsingtauense RIP1a and B. belcheri tsingtauense RIP1b activate NF-κB in a kinase activity-independent manner and induce apoptosis through the Fas-associated death domain protein-caspase cascade. Moreover, we found that the natural point mutation of Q to I in the RIP homotypic interaction motif of B. belcheri tsingtauense RIP1a provides negative feedback for amphioxus RIP1-mediated signaling. Thus, our study not only suggests that RIP1 has emerged as a molecular switch in triggering cell death or survival in a basal chordate, but also adds new insights into the regulation mechanisms of RIP1-related signaling, providing a novel perspective on human diseases mediated by RIP1.
  The Journal of Immunology 09/2011; 187(8):3962-71. · 5.79 Impact Factor
• Article: An improved nonchromatographic method for the purification of recombinant proteins using elastin-like polypeptide-tagged proteases.

  Dongming Lan, Guangrui Huang, Hongwei Shao, Lichun Zhang, Lixin Ma, Shangwu Chen, Anlong Xu
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  ABSTRACT: Proteins fused to the elastin-like polypeptide (ELP) tag can be selectively separated from crude cell extract without chromatography. To avoid the interference of the ELP tag on properties of the target protein, it is necessary to remove the ELP tag from target protein by protease digestion. Therefore, an additional chromatographic purification step is required to remove the proteases, and this is time- and labor-consuming. Here we demonstrate the utility of the ELP-tagged proteases for cleavage of ELP fusion proteins, allowing one-step removal of the cleaved ELP tag and ELP-tagged proteases without chromatography.
  Analytical Biochemistry 08/2011; 415(2):200-2. · 3.00 Impact Factor
• Article: Functional characterization of a ficolin-mediated complement pathway in amphioxus.

  Huiqing Huang, Shengfeng Huang, Yingcai Yu, Shaochun Yuan, Rui Li, Xin Wang, Hongchen Zhao, Yanhong Yu, Jun Li, Manyi Yang, Liqun Xu, Shangwu Chen, Anlong Xu
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  ABSTRACT: The ficolin-mediated complement pathway plays an important role in vertebrate immunity, but it is not clear whether this pathway exists in invertebrates. Here we identified homologs of ficolin pathway components from the cephalochordate amphioxus and investigated whether they had been co-opted into a functional ficolin pathway. Four of these homologs, ficolin FCN1, serine protease MASP1 and MASP3, and complement component C3, were highly expressed in mucosal tissues and gonads, and were significantly up-regulated following bacterial infection. Recombinant FCN1 could induce hemagglutination, discriminate among sugar components, and specifically recognize and aggregate several bacteria (especially gram-positive strains) without showing bactericidal activity. This suggested that FCN1 is a dedicated pattern-recognition receptor. Recombinant serine protease MASP1/3 formed complexes with recombinant FCN1 and facilitated the activation of native C3 protein in amphioxus humoral fluid, in which C3 acted as an immune effector. We conclude that amphioxus have developed a functional ficolin-complement pathway. Because ficolin pathway components have not been reported in non-chordate species, our findings supported the idea that this pathway may represent a chordate-specific innovation in the evolution of the complement system.
  Journal of Biological Chemistry 08/2011; 286(42):36739-48. · 4.77 Impact Factor
• Article: Differential genome-wide profiling of tandem 3' UTRs among human breast cancer and normal cells by high-throughput sequencing.

  Yonggui Fu, Yu Sun, Yuxin Li, Jie Li, Xingqiang Rao, Chong Chen, Anlong Xu
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  ABSTRACT: Tandem 3' UTRs produced by alternative polyadenylation (APA) play an important role in gene expression by impacting mRNA stability, translation, and translocation in cells. Several studies have investigated APA site switching in various physiological states; nevertheless, they only focused on either the genes with two known APA sites or several candidate genes. Here, we developed a strategy to study APA sites in a genome-wide fashion with second-generation sequencing technology which could not only identify new polyadenylation sites but also analyze the APA site switching of all genes, especially those with more than two APA sites. We used this strategy to explore the profiling of APA sites in two human breast cancer cell lines, MCF7 and MB231, and one cultured mammary epithelial cell line, MCF10A. More than half of the identified polyadenylation sites are not included in human poly(A) databases. While MCF7 showed shortening 3' UTRs, more genes in MB231 switched to distal poly(A) sites. Several gene ontology (GO) terms and pathways were enriched in the list of genes with switched APA sites, including cell cycle, apoptosis, and metabolism. These results suggest a more complex regulation of APA sites in cancer cells than previously thought. In short, our novel unbiased method can be a powerful approach to cost-effectively investigate the complex mechanism of 3' UTR switching in a genome-wide fashion among various physiological processes and diseases.
  Genome Research 05/2011; 21(5):741-7. · 13.61 Impact Factor
• Article: Structure-function relationship of conotoxin lt14a, a potential analgesic with low cytotoxicity.

  Dandan Sun, Zhenghua Ren, Xiayun Zeng, Yuwen You, Wuguang Pan, Maojun Zhou, Lei Wang, Anlong Xu
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  ABSTRACT: A novel conotoxin lt14a containing 13 amino acid residues with an amidated C-terminus derived from Conus litteratus, belongs to C-C-C-C cysteine pattern. As the smallest peptide of conotoxin framework 14, lt14a could inhibit nicotinic acetylcholine receptor and suppress pain. To elucidate structure-function relationship, we determine the solution structure by NMR and find that lt14a comprises a short duple β-strand region and β-turn motif. An analog [K7A]-lt14a of Ala substitution for Lys in position 7 is designed. Interestingly, [K7A]-lt14a exhibits higher activity than lt14a as long-lasting analgesic in the hotplate pain model in mice. Additionally, MTT assay reveals that the two peptides have low toxicity to human cells. The studies suggest that positively charged residue may not be involved in the blocking mechanism. However, due to the Ala substitution, hydrophobic residues' patch expansion strengthens the binding ability. A hypothesis is given that in conotoxin lt14a, hydrophobic residues rather than charged residues play a key role during target binding.
  Peptides 02/2011; 32(2):300-5. · 2.43 Impact Factor
• Article: The evolution and regulation of the mucosal immune complexity in the basal chordate amphioxus.

  Shengfeng Huang, Xin Wang, Qingyu Yan, Lei Guo, Shaochun Yuan, Guangrui Huang, Huiqing Huang, Jun Li, Meiling Dong, Shangwu Chen, Anlong Xu
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  ABSTRACT: Both amphioxus and the sea urchin encode a complex innate immune gene repertoire in their genomes, but the composition and mechanisms of their innate immune systems, as well as the fundamental differences between two systems, remain largely unexplored. In this study, we dissect the mucosal immune complexity of amphioxus into different evolutionary-functional modes and regulatory patterns by integrating information from phylogenetic inferences, genome-wide digital expression profiles, time course expression dynamics, and functional analyses. With these rich data, we reconstruct several major immune subsystems in amphioxus and analyze their regulation during mucosal infection. These include the TNF/IL-1R network, TLR and NLR networks, complement system, apoptosis network, oxidative pathways, and other effector genes (e.g., peptidoglycan recognition proteins, Gram-negative binding proteins, and chitin-binding proteins). We show that beneath the superficial similarity to that of the sea urchin, the amphioxus innate system, despite preserving critical invertebrate components, is more similar to that of the vertebrates in terms of composition, expression regulation, and functional strategies. For example, major effectors in amphioxus gut mucous tissue are the well-developed complement and oxidative-burst systems, and the signaling network in amphioxus seems to emphasize signal transduction/modulation more than initiation. In conclusion, we suggest that the innate immune systems of amphioxus and the sea urchin are strategically different, possibly representing two successful cases among many expanded immune systems that arose at the age of the Cambrian explosion. We further suggest that the vertebrate innate immune system should be derived from one of these expanded systems, most likely from the same one that was shared by amphioxus.
  The Journal of Immunology 02/2011; 186(4):2042-55. · 5.79 Impact Factor
• Article: Identification and expression of amphioxus AmphiSmad1/5/8 and AmphiSmad4.

  Xuesong Yu, Jianwei Li, Hui Liu, Xiaodan Li, Shangwu Chen, Hongwei Zhang, Anlong Xu
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  ABSTRACT: Smad family proteins are identified as intracellular signal mediators of the TGF-β superfamily. In this study, we identified two novel members of the Smad family, termed as AmphiSmad1/5/8 and AmphiSmad4, from Chinese amphioxus. Both AmphiSmad1/5/8 and AmphiSmad4 showed a typical domain structure of Smad proteins consisting of conserved MH1 and MH2 domains. Phylogenetic analysis placed AmphiSmad1/5/8 in the Smad1, 5 and 8 subgroup of the R-Smad subfamily, and AmphiSmad4 in the Co-Smad subfamily. The spatial and temporal gene expression patterns of AmphiSmad1/5/8 and AmphiSmad4 showed that they may be involved in the embryonic development of notochord, myotome and alimentary canal, and may help to establish the specification of dorsal-ventral axis of amphioxus. Moreover, AmphiSmad1/5/8 and AmphiSmad4 showed extensive distribution in all adult tissues examined, suggesting that these two genes may play important roles in the morphogenesis of a variety of tissues especially notochord and gonad.
  Science China. Life sciences 01/2011; 54(3):220-6. · 2.02 Impact Factor
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  Available from: PubMed Central

  Article: HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.

  Benrong Liu, Yonggui Fu, Zhifen Wang, Sisi Zhou, Yu Sun, Yuping Wu, Anlong Xu
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  ABSTRACT: HLA-DRB1 is the most polymorphic MHC (major histocompatibility complex) class II gene in human, and plays a crucial role in the development and function of the immune system. Extensive polymorphisms exist in the promoter and 3'-UTR of HLA-DRB1, especially a LTR (Long terminal repeat) element in the promoter, which may be involved in the expression regulation. However, it remains unknown how the polymorphisms in the whole promoter region and 3'-UTR to regulate the gene expression. In this study, we investigated the extensive polymorphisms in the HLA-DRB1 promoter and 3'-UTR, and how these polymorphisms affect the gene expression in both independent and jointly manners. It was observed that most of the haplotypes in the DRB1 promoter and 3'-UTR were clustered into 4 conserved lineages (H1, H2, H3 and H4), and showed high linkage disequilibrium. Compared with H1 and H2 lineage, a LTR element in the promoter of H3 and H4 lineage significantly suppressed the promoter activity, whereas the activity of the linked 3'-UTR increased, leading to no apparent difference in the final expression product between H1/H2 and H3/H4 lineage. Nevertheless, compared with the plasmid with a promoter and 3'-UTR from the same lineage, the recombinant plasmid with a promoter from H2 and a 3'-UTR from H3 showed about double fold increased luciferase activity, Conversely, the recombinant plasmid with a promoter from H3 and a 3'-UTR from H2 resulted in about 2-fold decreased luciferase activity. These results indicate that the promoter and 3'-UTR of HLA-DRB1 may antagonistically regulate the gene expression, which may be subjected to stabilizing selection. These findings may provide a novel insight into the mechanisms of the diseases associated with HLA-DRB1 genes.
  PLoS ONE 01/2011; 6(10):e25794. · 4.09 Impact Factor