Background: Early treatment is key for optimizing the therapeutic success of drugs, and the current initiating treatment that blocks the progression of bone destruction during the pre-arthritic stages remains unsatisfactory. The microbial disorder in rheumatoid arthritis (RA) patients is significantly reversed with effective treatment. Modulating aberrant gut microbiomes into a healthy state is a potential therapeutic approach for preventing bone damage. Results: By using metagenomic shotgun sequencing and a metagenome-wide association study, we assessed the effect of Lactobacillus casei (L. casei) on the induction of arthritis as well as on the associated gut microbiota and immune disorders in adjuvant-induced arthritis (AIA) rats. Treatment of AIA rats with L. casei inhibited joint swelling, lowered arthritis scores, and prevented bone destruction. Along with the relief of arthritis symptoms, dysbiosis in the microbiome of arthritic rats was significantly reduced after L. casei intervention. The relative abundance of AIA-decreased Lactobacillus strains, including Lactobacillus hominis, Lactobacillus reuteri, and Lactobacillus vaginalis, were restored to normal and Lactobacillus acidophilus was upregulated by the administration of L. casei to the AIA rats. Moreover, L. casei downregulated the expression of pro-inflammatory cytokines, which are closely linked to the effect of the L. casei treatment-associated microbes. Functionally, the maintenance of the redox balance of oxidative stress was involved in the improvement in the L. casei-treated AIA rats. Conclusion: A single bacterium, L. casei (ATCC334), was able to significantly suppress the induction of AIA and protect bones from destruction in AIA rats by restoring the microbiome dysbiosis in the gut, indicating that using probiotics may be a promising strategy for treating RA, especially in the early stage of the disease.

Hudan Pan;Ruijin Guo;Yanmei Ju;Qi Wang;Jie Zhu;Ying Xie;Yanfang Zheng;Ting Li;Zhongqiu Liu;Linlin Lu;Fei Li;Bin Tong;Liang Xiao;Xun Xu;Elaine Lai Han Leung;Runze Li;焕明 杨;Jian Wang;Hua Zhou;Huijue Jia;Liang Liu

Microbiome

2019-7-17

In plants, parasitism triggers the reductive evolution of plastid genomes (plastomes). To disentangle the molecular evolutionary associations between feeding on other plants below-or aboveground and general transitions from facultative to obligate parasitism, we analyzed 34 complete plastomes of autotrophic, root-and stem-feeding hemiparasitic, and holoparasitic Santalales. We observed inexplicable losses of housekeeping genes and tRNAs in hemiparasites and dramatic genomic reconfiguration in holoparasitic Balanophoraceae, whose plastomes have exceptionally low GC contents. Genomic changes are related primarily to the evolution of hemi-or holoparasitism, whereas the transition from a root-to a stem-feeding mode plays no major role. In contrast, the rate of molecular evolution accelerates in a stepwise manner from autotrophs to root-and then stem-feeding parasites. Already the ancestral transition to root-parasitism coincides with a relaxation of selection in plastomes. Another significant selectional shift in plastid genes occurs as stem-feeders evolve, suggesting that this derived form coincides with trophic specialization despite the retention of photosynthetic capacity. Parasitic Santalales fill a gap in our understanding of parasitism-Associated plastome degeneration. We reveal that lifestyle-genome associations unfold interdependently over trophic specialization and feeding mode transitions, where holoparasitic Balanophoraceae provide a system for exploring the functional realms of plastomes.

Xiaoli Chen;Dongming Fang;Chenyu Wu;Bing Liu;Yang Liu;Sunil Kumar Sahu;Bo Song;Shuai Yang;Tuo Yang;Jinpu Wei;Xuebing Wang;Wen Zhang;Qiwu Xu;Huafeng Wang;Langxing Yuan;Xuezhu Liao;Lipeng Chen;Ziqiang Chen;Fu Yuan;Yue Chang;Lihua Lu;焕明 杨;Jian Wang;Xun Xu;Xin Liu;Susann Wicke;Huan Liu

Genome Biology and Evolution

2019-12-16

Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested as a marker of prognosis and response to treatment in breast cancer. In vitro, TIMP-1 can regulate shedding of the extracellular domain of HER2 and signalling via the Akt pathway, and we hypothesize that TIMP-1 therefore can affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level of TIMP-1 protein. Western blotting showed that the activation of Akt, PTEN, and HER2 as well as ADAM10 was similar in all clones. In conclusion, in this model, TIMP-1 overexpression does not affect HER2 cleavage by ADAM10 or signalling via the Akt pathway, and TIMP-1 does not influence sensitivity to trastuzumab and lapatinib.

Xiaohong Deng;Louise Fogh;Ulrik Lademann;Vibeke Jensen;Jan Stenvang;焕明 杨;Nils Brünner;Anne Sofie Schrohl

Tumor Biology

2013-4

Background: There is a rapidly increasing amount of de novo genome assembly using next-generation sequencing (NGS) short reads; however, several big challenges remain to be overcome in order for this to be efficient and accurate. SOAPdenovo has been successfully applied to assemble many published genomes, but it still needs improvement in continuity, accuracy and coverage, especially in repeat regions.Findings: To overcome these challenges, we have developed its successor, SOAPdenovo2, which has the advantage of a new algorithm design that reduces memory consumption in graph construction, resolves more repeat regions in contig assembly, increases coverage and length in scaffold construction, improves gap closing, and optimizes for large genome. Conclusions: Benchmark using the Assemblathon1 and GAGE datasets showed that SOAPdenovo2 greatly surpasses its predecessor SOAPdenovo and is competitive to other assemblers on both assembly length and accuracy. We also provide an updated assembly version of the 2008 Asian (YH) genome using SOAPdenovo2. Here, the contig and scaffold N50 of the YH genome were ~20.9 kbp and ~22 Mbp, respectively, which is 3-fold and 50-fold longer than the first published version. The genome coverage increased from 81.16% to 93.91%, and memory consumption was ~2/3 lower during the point of largest memory consumption.

Ruibang Luo;Binghang Liu;Yinlong Xie;Zhenyu Li;Weihua Huang;Jianying Yuan;Guangzhu He;Yanxiang Chen;Qi Pan;Yunjie Liu;Jingbo Tang;Gengxiong Wu;Hao Zhang;Yujian Shi;Yong Liu;Chang Yu;Bo Wang;Yao Lu;Changlei Han;David W. Cheung;Siu Ming Yiu;Shaoliang Peng;Zhu Xiaoqian;Guangming Liu;湘科 廖;Yingrui Li;焕明 杨;Jian Wang;Tak Wah Lam;军 王

GigaScience

2012-12-27

Quality control (QC) and preprocessing are essential steps for sequencing data analysis to ensure the accuracy of results. However, existing tools cannot provide a satisfying solution with integrated comprehensive functions, proper architectures, and highly scalable acceleration. In this article, we demonstrate SOAPnuke as a tool with abundant functions for a "QC-Preprocess-QC" workflow and MapReduce acceleration framework. Four modules with different preprocessing functions are designed for processing datasets from genomic, small RNA, Digital Gene Expression, and metagenomic experiments, respectively. As a workflow-like tool, SOAPnuke centralizes processing functions into 1 executable and predefines their order to avoid the necessity of reformatting different files when switching tools. Furthermore, the MapReduce framework enables large scalability to distribute all the processing works to an entire compute cluster. We conducted a benchmarking where SOAPnuke and other tools are used to preprocess a ~30× NA12878 dataset published by GIAB. The standalone operation of SOAPnuke struck a balance between resource occupancy and performance. When accelerated on 16 working nodes with MapReduce, SOAPnuke achieved ~5.7 times the fastest speed of other tools.

Yuxin Chen;Yongsheng Chen;Chunmei Shi;Zhibo Huang;Yong Zhang;Shengkang Li;Yan Li;Jia Ye;Chang Yu;Zhuo Li;Xiuqing Zhang;Jian Wang;焕明 杨;Lin Fang;Qiang Chen

GigaScience

2018-1-1

Using a magnetic beads-mediated cDNA selection procedure and a fetal brain expression library, we identified a transcriptional unit within a cosmid positive for the marker D11S384. Pursuit of its full-length cDNA led to the cloning of the third candidate gene (CAND3) we studied in our quest for the ataxia-telangiectasia (A-T) gene, ATM. CAND3 spans ~140 kb of genomic DNA and is located immediately centrimeric to ATM, with 544 bp of DNA separating the two genes. CAND3 encodes two ubiquitously expressed transcripts of ~5.8 kb and ~4.6 kb that are divergently transcribed from a promoter region common to ATM. Nucleotide sequence was determined for one of its alternately spliced transcripts. The predicted protein has 1175 amino acids and is novel in sequence, with only weak homologies to transcriptional factors, nucleoporin protein, and protein kinases, including members of the phosphatidylinositol 3-kinase (PI-3 kinase) family. Although neither homology to ATM nor any mutation of CAND3 in A-T patients has been found, the head-to-head arrangement of CAND3 and ATM, with expression of both housekeeping genes from a common stretch of 544 bp intergenic DNA, suggests a bi-directional promoter possibly for co-regulation of biologically related functions. YACs, BACs, cosmids, and STSs are defined to aid in the further study of this gene.

Xiaeguang Chen;Lan Yang;Nitin Udar;Teresa Liang;Nancy Uhrhammer;Shunbin Xu;Jacques Olivier Bay;Zhijun Wang;Suganda Dandakar;Sujata Chiplunkar;Ivana Klisak;Milhan Telatar;焕明 杨;Patrick Concannon;Richard A. Gatti

Mammalian Genome

1997-2

Figure 1c. is with numeric error. The error can not result in any change of discussion and conclusion. The proper figures corresponding to Fig 1c are in supplement file, see figure 5 and 6.

Yingying Zhao;Shenmin Guan;Wenhui Song;Yongping Li;Lizhen Ling;Yu Wang;Xinshu Li;Lili Qin;Haijing Yu;焕明 杨;Jian Wang;Jinlong Yang;Jin Liu;Le Cheng

Annals of Hematology

2018-1-1

Background: Japanese quail (Coturnix japonica), a recently domesticated poultry species, is important not only as an agricultural product, but also as a model bird species for genetic research. However, most of the biological questions concerning genomics, phylogenetics, and genetics of some important economic traits have not been answered. It is thus necessary to complete a high-quality genome sequence as well as a series of comparative genomics, evolution, and functional studies. Results: Here, we present a quail genome assembly spanning 1.04 Gb with 86.63% of sequences anchored to 30 chromosomes (28 autosomes and 2 sex chromosomes Z/W). Our genomic data have resolved the long-term debate of phylogeny among Perdicinae (Japanese quail), Meleagridinae (turkey), and Phasianinae (chicken). Comparative genomics and functional genomic data found that four candidate genes involved in early maturation had experienced positive selection, and one of them encodes follicle stimulating hormone beta (FSHβ), which is correlated with different FSHβ levels in quail and chicken. We re-sequenced 31 quails (10 wild, 11 egg-type, and 10 meat-type) and identified 18 and 26 candidate selective sweep regions in the egg-type and meat-type lines, respectively. That only one of them is shared between egg-type and meat-type lines suggests that they were subject to an independent selection. We also detected a haplotype on chromosome Z, which was closely linked with maroon/yellow plumage in quail using population resequencing and a genome-wide association study. This haplotype block will be useful for quail breeding programs. Conclusions: This study provided a high-quality quail reference genome, identified quail-specific genes, and resolved quail phylogeny. We have identified genes related to quail early maturation and a marker for plumage color, which is significant for quail breeding. These results will facilitate biological discovery in quails and help us elucidate the evolutionary processes within the Phasianidae family.

Yan Wu;Yaolei Zhang;Zhuocheng Hou;Guangyi Fan;Jinsong Pi;Shuai Sun;Jiang Chen;Huaqiao Liu;Xiao Du;Jie Shen;Gang Hu;Wenbin Chen;Ailuan Pan;Pingping Yin;Xiaoli Chen;Yuejin Pu;He Zhang;Zhenhua Liang;Jianbo Jian;Hao Zhang;Bin Wu;Jing Sun;Jianwei Chen;Hu Tao;Ting Yang;Hongwei Xiao;Huan Yang;Chuanwei Zheng;Mingzhou Bai;Xiaodong Fang;David W. Burt;Wen Wang;Qingyi Li;Xun Xu;Chengfeng Li;焕明 杨;Jian Wang;宁 杨;Xin Liu;Jinping Du

GigaScience

2018-5-1

Here we present the genome sequence and annotation of the wild olive tree (Olea europaea var. sylvestris), called oleaster, which is considered an ancestor of cultivated olive trees. More than 50,000 protein-coding genes were predicted, a majority of which could be anchored to 23 pseudochromosomes obtained through a newly constructed genetic map. The oleaster genome contains signatures of two Oleaceae lineage-specific paleopolyploidy events, dated at ∼28 and ∼59 Mya. These events contributed to the expansion and neofunctionalization of genes and gene families that play important roles in oil biosynthesis. The functional divergence of oil biosynthesis pathway genes, such as FAD2, SACPD, EAR, and ACPTE, following duplication, has been responsible for the differential accumulation of oleic and linoleic acids produced in olive compared with sesame, a closely related oil crop. Duplicated oleaster FAD2 genes are regulated by an siRNA derived from a transposable element-rich region, leading to suppressed levels of FAD2 gene expression. Additionally, neofunctionalization of members of the SACPD gene family has led to increased expression of SACPD2, 3, 5, and 7, consequently resulting in an increased desaturation of steric acid. Taken together, decreased FAD2 expression and increased SACPD expression likely explain the accumulation of exceptionally high levels of oleic acid in olive. The oleaster genome thus provides important insights into the evolution of oil biosynthesis and will be a valuable resource for oil crop genomics.

Turgay Unver;Zhangyan Wu;Lieven Sterck;Mine Turktas;Rolf Lohaus;Zhen Li;Ming Yang;Lijuan He;Tianquan Deng;Francisco Javier Escalante;Carlos Llorens;Francisco J. Roig;Iskender Parmaksiz;Ekrem Dundar;Fuliang Xie;Baohong Zhang;Arif Ipek;Serkan Uranbey;Mustafa Erayman;Emre Ilhan;Oussama Badad;Hassan Ghazal;David A. Lightfoot;Pavan Kasarla;Vincent Colantonio;Huseyin Tombuloglu;Pilar Hernandez;Nurengin Mete;Oznur Cetin;Marc Van Montagu;焕明 杨;Qiang Gao;Gabriel Dorado;Yves Van de Peer

Proceedings of the National Academy of Sciences of the United States of America

2017-10-31

In this work, severe acute respiratory syndrome associated coronavirus (SARS-CoV) genome BJ202 (AY864806) was completely sequenced. The genome was directly accessed from the stool sample of a patient in Beijing. Comparative genomics methods were used to analyze the sequence variations of 116 SARS-CoV genomes (including BJ202) available in the NCBI GenBank. With the genome sequence of GZ02 as the reference, there were 41 polymorphic sites identified in BJ202 and a total of 278 polymorphic sites present in at least two of the 116 genomes. The distribution of the polymorphic sites was biased over the whole genome. Nearly half of the variations (50.4%, 140/278) clustered in the one third of the whole genome at the 3′ end (19.0 kb-29.7 kb). Regions encoding Orf10-11, Orf3/4, E, M and S protein had the highest mutation rates. A total of 15 PCR products (about 6.0 kb of the genome) including 11 fragments containing 12 known polymorphic sites and 4 fragments without identified polymorphic sites were cloned and sequenced. Results showed that 3 unique polymorphic sites of BJ202 (positions 13 804, 15 031 and 20 792) along with 3 other polymorphic sites (26 428, 26 477 and 27 243) all contained 2 kinds of nucleotides. It is interesting to find that position 18379 which has not been identified to be polymorphic in any of the other 115 published SARS-CoV genomes is actually a polymorphic site. The nucleotide composition of this site is A (8) to G (6). Among 116 SARS-CoV genomes, 18 types of deletions and 2 insertions were identified. Most of them were related to a 300 bp region (27 700-28 000) which encodes parts of the putative ORF9 and ORF10-11. A phylogenetic tree illustrating the divergence of whole BJ202 genome from 115 other completely sequenced SARS-CoVs was also constructed. BJ202 was phylogeneticly closer to BJ01 and LLJ-2004.

Lei Shang;Yan Qi;Qi Yu Bao;Wei Tian;Jian Cheng Xu;明光 冯;焕明 杨

Journal of Genetics and Genomics

2006-4