Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strai...Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10 236 715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9 228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel 'quasicore' with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.展开更多
In this study, the 454 pyrosequencing technology was used to analyze the DNA of the Microcystis aeruginosa symbiosis system from cyanobacterial algal blooms in Taihu Lake, China. We generated 183 228 reads with an ave...In this study, the 454 pyrosequencing technology was used to analyze the DNA of the Microcystis aeruginosa symbiosis system from cyanobacterial algal blooms in Taihu Lake, China. We generated 183 228 reads with an average length of 248 bp. Running the 454 assembly algorithm over our sequences yielded 22 239 significant contigs. After excluding the M. aeruginosa sequences, we obtained 1 322 assembled contigs longer than 1 000 bp. Taxonomic analysis indicated that four kingdoms were represented in the community: Archaea (n = 9; 0.01%), Bacteria (n = 98 921; 99.6%), Eukaryota (n = 373; 3.7%), and Viruses (n = 18; 0.02%). The bacterial sequences were predominantly Alphaproteobacteria (n = 41 805; 83.3%), Betaproteobacteria (n = 5 254; 10.5%) and Gammaproteobacteria (n = 1 180; 2.4%). Gene annotations and assignment of COG (clusters of orthologous groups) functional categories indicate that a large number of the predicted genes are involved in metabolic, genetic, and environmental information processes. Our results demonstrate the extraordinary diversity of a microbial community in an ectosymbiotic system and further establish the tremendous utility of pyrosequencing.展开更多
Objective To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. Methods Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC...Objective To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. Methods Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC5180) were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. Results The Hunter-Gaston Index (HGI) for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. boris and M. africanum strains from the four loci. Conclusion We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.展开更多
Objective: To evaluate the effects of polymorphisms in TLR7 and TLRS(as potential candidate genes) on asthma risk and asthma-related phenotypes. Methods: We consecutively recruited 318 unrelated adult asthmatic pa...Objective: To evaluate the effects of polymorphisms in TLR7 and TLRS(as potential candidate genes) on asthma risk and asthma-related phenotypes. Methods: We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results: The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males (adjusted ORs = 0.126, 95% CIs = 0.016-0.995). The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis (adjusted ORs = 0.18, 95% CIs = 0.04-0.90). The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion:TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.展开更多
Objective: To investigate the effect of insulin-like growth factor 1 receptor (IGF1R) small interfering RNA (siRNA) on the growth of human liver cancer SMMC7721 cell xenograft in nude mice. Methods: siRNA target...Objective: To investigate the effect of insulin-like growth factor 1 receptor (IGF1R) small interfering RNA (siRNA) on the growth of human liver cancer SMMC7721 cell xenograft in nude mice. Methods: siRNA targeting IGF1R was designed, and plasmid SMMC7721-1GF1R-siRNA was constructed and transfected into SMMC7721 cells (SMMC7721-1GF1R-siRNA cells); the cells transfected with SMMC7721-1GF1 R-mutation (SMMC7721-1GF1 R-mutation cells) were used as negative con- trol, and untransfected cells as empty control. Stable cell clones were screened by G418, and transplanted into nude mice to establish cancer xenograft. Tumor growth was monitored. Tumor morphology was observed with HE staining. The expression of IGF1R protein in tumor tissues was detected by Western blot. Microvessel density (MVD) in tumor tissues was detected by SP immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Results: The tumor volume was significantly smaller in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (P 〈 0.05). Necrosis and cell apoptosis were found in SMMC7721- IGF1R-siRNA group. The expression of IGF1R protein was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (P 〈 0.05). MVD was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (11.3 ± 4.4 vs. 36.7 ± 7.6 and 28.4 ±6.5, P 〈 0.05). The apoptosis rate of tumor cells was significantly higher in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups [(50.2 ± 6.4)% vs. (5.4 ± 1.0)% or (6.0 ±2.1)%, P〈0.05]. Conclusion: IGF1R siRNA can inhibit the growth of SMMC7721 cell xenograft in nude mice.展开更多
Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta, COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21- 22 and COLIA2 at 7q22.1. T...Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta, COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21- 22 and COLIA2 at 7q22.1. The Linkage ( Version 5. 1 ) was used for 2-point analysis. DNA sequencing was used to screen and identify the mutation. Results A linkage to the markers on chromosome 17q21-22 was observed. Se- quence analysis of COLIA1 revealed a splicing mutation (IVSS-2A 〉 G) that converted the 3' end of intron 8 from AG to GG. Conclusion This mutation ( IVS 8-2A 〉 G) is novel, and has not yet been registered in the Human Type I and Type Ⅲ Collagen Mutations Database.展开更多
BACKGROUND The diagnostic and economic value of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale.AIM To reassess the d...BACKGROUND The diagnostic and economic value of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale.AIM To reassess the diagnostic and economic value of the three tumor biomarkers.METHODS A retrospective analysis of all 32857 subjects who underwent CEA,CA19-9,CA72-4,gastroscopy and colonoscopy from October 2006 to May 2018 was conducted.Then,we assessed the discrimination and clinical usefulness.Total cost,cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes(gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive).RESULTS The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer(CRC),while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers(GICs).Regarding early diagnosis,only CEA could be used for early CRC.The combination of biomarkers didn’t greatly increase the area under the curve.The economic indicators of CEA were superior to those of CA19-9,CA72-4 and any combination.At the threshold of 1.8μg/L to 10.4μg/L,all four indicators of CEA were lower than those in the scheme that conducted gastrointestinal endoscopy only.Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable.CONCLUSION CEA had qualified diagnostic value for CRC and superior economic value for GICs,especially for elderly health checkup subjects.CA72-4 was not suitable as a diagnostic biomarker.展开更多
Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related death. More than 80% of diagnoses occur at the middle to late stage of the disease, highlighting an urgent ne...Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related death. More than 80% of diagnoses occur at the middle to late stage of the disease, highlighting an urgent need for novel biomarkers detectable at earlier stages. Recently, aberrantly expressed microRNAs (miRNAs) have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis. This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013. Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis, tumor proliferation, distant metastasis and invasion. Furthermore, tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing. As miRNAs in plasma/serum are well protected from RNases, they remain stable under harsh conditions. Thus, potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection. Circulating miRNAs, as well as tissue miRNAs, may allow for the detection of gastric cancer at an early stage, prediction of prognosis, and monitoring of recurrence and/or lymph node metastasis. Taken together, the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and ri...AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS:One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS:In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels ≥ 104 to < 105; ≥ 105 to < 106; ≥ 106 to < 107; ≥ 107 copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.CONCLUSION:The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 104-107 range.展开更多
Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira that infects humans and a wide range of animals. By combining computational prediction and high-accuracy tandem m...Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira that infects humans and a wide range of animals. By combining computational prediction and high-accuracy tandem mass spectra, we revised the genome annotation of Leptospira interrogans serovar Lai, a free-living pathogenic spirochete responsible for leptospirosis, providing substantial peptide evidence for novel genes and new gene boundaries. Subsequently, we presented a high-coverage proteome analysis of protein expression and multiple posttranslational modifications (PTMs). Approximately 64.3% of the predicted L. interrogans proteins were cataloged by detecting 2 540 proteins. Meanwhile, a profile of multiple PTMs was concurrently established, containing in total 32 phosphorylated, 46 acetylated and 155 methylated proteins. The PTM systems in the serovar Lai show unique features. Unique eukaryotic-like features of L. interrogans protein modifications were demonstrated in both phosphorylation and arginine methylation. This systematic analysis provides not only comprehensive information of high-coverage protein expression and multiple modifications in prokaryotes but also a view suggesting that the evolutionarily primitive L. interrogans shares significant similarities in protein modification systems with eukaryotes.展开更多
The goal of the Human Genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromo...The goal of the Human Genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromosome 3 as its share of this historic project, referred as “Beijing Region”. The complete sequence of this region comprises of 17.4 megabasepairs (Mb) with an average GC content of 42% and an average recombination rate of 2.14 cM/Mb. Within Beijing Region, 122 known and 20 novel genes are identified, as well as 42607 single nucleotide polymorphisms (SNPs). Comprehensive analyses also reveal: (i) gene density and GC-content of Beijing Region are in agreement with human cytogenetic maps, i.e. G-minus bands are GC-rich and of a high gene density, whereas G-plus bands are GC-poor and of a relatively low gene density; (ii) the average recombination rate within Beijing Region is rela-tively high compared with other regions of chromosome 3, with the highest recombination rate of 6.06 cM/Mb in the subtelomeric area; (iii) it is most likely that a large gene, associated with the mammary gland, may reside in the 1.1 Mb gene-poor area near the telomere; (iv) many dis-ease-related genes are genetically mapped to Beijing Region, including those associated with cancers and metabolic syndromes. All make Beijing Region an important target for in-depth mo-lecular investigations with a purpose of medical applications.展开更多
The amino acid biosynthesis and proteolytic system of Lactobacillus bulgaricus (L.Bulgaricus ) is important for its growth in niche-specific environments, as well as for flavour formation in the food industry. Compara...The amino acid biosynthesis and proteolytic system of Lactobacillus bulgaricus (L.Bulgaricus ) is important for its growth in niche-specific environments, as well as for flavour formation in the food industry. Comparative analyses of 4 completed sequences of the L.Bulgaricus strain genome on a genomic scale revealed that genes involved in amino acids synthesis were undergoing reductive evolution. However, the selected industrial strains, namely, L.Bulgaricus 2038 and L.Bulgaricus ND02, retained more complete genes in the amino acid synthesis and proteolytic system category than the laboratory strains, and have some unique genes and pathways for obtaining amino acids that enable these bacteria to adapt to their various environmental niches.展开更多
BACKGROUND: Studies have shown that adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene influences atherosclerosis. Studies have also demonstrated that cerebral infarction does not occur often in pre...BACKGROUND: Studies have shown that adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene influences atherosclerosis. Studies have also demonstrated that cerebral infarction does not occur often in pre-menopausal women. It has been, therefore, assumed that sex plays a role in R219K polymorphism of ABCA1 gene and cerebral infarction. OBJECTIVE: To explore the relationship between lipid metabolism-correlated R219K polymorphism of ABCA1 gene, risk factors of cerebral infarction and lipid level, and to determine whether there were significant differences in gender between R219K polymorphism of ABCA1 gene and cerebral infarction. DESIGN, TIME AND SETTING: A multicentral and non-randomized, controlled study based on gene polymorphism was performed at the Chinese National Human Genome Center, and lipid concentrations were measured at Beijing Xuanwu Hospital. Patients with cerebral infarction and healthy subjects were enrolled from eight hospitals of six provinces of China between October 2002 and December 2004. PARTICIPANTS: There were 177 patients in the cerebral infarction group, including 119 males and 58 females, with a mean age of (60 -+ 13) years, and 234 healthy subjects in the normal control group, including 79 males and 155 females, with a mean age of (58 ± 12) years. METHODS: R219K polymorphism of the ABCA1 gene was detected using polymerase chain reaction-restriction fragment length polymorphism, and blood lipid concentrations were simultaneously measured. MAIN OUTCOME MEASURES: Genotype and allele frequency of R219K polymorphic site, and blood lipid concentrations. RESULTS: RR genotype and R allele frequency of males in the cerebral infarction were significantly greater than males in the normal control group [RR genotype: x2 = 5.305, OR (95% CO, 2.326 (1.120 4.828), P〈 0.05; R allele: x2= 4.219, OR (95% CO, 1.528 (1.019 2.292), P〈 0.05]. In addition, RR genotype and R allele frequency of males were significantly greater than females in the cerebral infarction group [RR genotype: x2= 5.172, OR (95% C/), 2.604 (1.120-6.057), P〈 0.05; R allele: x2= 4.818, OR (95% CO, 1.652 (1.053 2.589), P〈 0.05]. There were no significant differences between genotype and lipid concentrations between the two groups (P〉 0.05). CONCLUSION: The RR genotype of ABCA1 R219K might be associated with onset of cerebral infarction in males, but blood lipid concentrations do not relate to R219K polymorphism.展开更多
Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of...Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.Methods The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.Results Black males were diagnosed at a later stage, more commonly with local or distant metastases.The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival(OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.Conclusion Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.展开更多
Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-m...Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemi- sinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on compre- hensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the chal- lenge of increasing global demand of artemisinin.展开更多
We conducted a genome-wide scan, in which 358 well distributed fluorescent dye-labeled microsatellite marker sets were applied in 32 Chinese Han type 2 diabetes families from Northern China to search for the susceptib...We conducted a genome-wide scan, in which 358 well distributed fluorescent dye-labeled microsatellite marker sets were applied in 32 Chinese Han type 2 diabetes families from Northern China to search for the susceptibility gene loci. The data collected from screening all the chromosomes of genome were genotyped by using genescan and genotyping software, then, parametric and non-parametric multipoint test, and affected sib-pair analysis as well, were used to analyze the data. We identified some susceptibility gene loci residing in chromosomes 1,12,18,20, respectively, or precisely, located around D1S214, D1S207, D1S218, D1S235, D12S336, D18S61 and D20S118. The comparison of this result with those from other regions and races reflected the complexity and heterogeneity of type 2 diabetes.展开更多
Ketogulonigenium sp. may convert L-sorbose into 2-keto-L-gulonic acid, the vitamin C precursor. The genome of Ketogulonigenium sp. WB0104 consists of a circular 2765030 bp chromo- some with 61.69% G+C content and two ...Ketogulonigenium sp. may convert L-sorbose into 2-keto-L-gulonic acid, the vitamin C precursor. The genome of Ketogulonigenium sp. WB0104 consists of a circular 2765030 bp chromo- some with 61.69% G+C content and two circular plasmids of 267968 and 242707 bp. The genome contains 2727 open reading frames (ORFs). The systems of replication, transcription, translation, carbohydrate and energy metabolism are intact, but the repair system is incomplete. About 640 predicted ORFs have been found to encode transporter pro- teins, which account for about one fourth of total predicted ORFs, noticeably higher than other docu- mented bacteria. This may be due to the fact that WB0104 adapts to soil circumstance.展开更多
Acidithiobacillus caldus is one of the dominant sulfur-oxidizing bacteria in bioleaching reactors. It plays the essential role in maintaining the high acidity and oxidation of reduced inorganic sulfur compounds during...Acidithiobacillus caldus is one of the dominant sulfur-oxidizing bacteria in bioleaching reactors. It plays the essential role in maintaining the high acidity and oxidation of reduced inorganic sulfur compounds during bioleaching process. In this report, the complete genome sequence of A. caldus SM-1 is presented. The genome is composed of one chromosome (2,932,225 bp) and four plasmids (pLAtcl, pLAtc2, pLAtc3, pLAtcm) and it is rich in repetitive sequences (accounting for 11% of the total genome), which are often associated with transposable genetic elements. In particular, twelve copies of ISAtfe and thirty-seven copies of ISAtcl have been identified, suggesting that they are active transposons in the genome. A. caldus SM-1 encodes all enzymes for the central metabolism and the assimilation of carbon compounds, among which 29 proteins/enzymes were identifiable with proteomic tools. The SM-1 fixes CO2 via the classical Calvin-Bassham--Benson (CBB) cycle, and can operate complete Embden-Meyerhof pathway (EMP), pentose phosphate pathway (PPP), and gluconeogenesis. It has an incomplete tricarboxylic acid cycle (TCA). Four putative transporters involved in carbohydrate uptake were identified. Taken together, the results suggested that SM-1 was able to assimilate carbohydrates and this was subsequently confirmed experimentally because addition of 1% glucose or sucrose in basic salt medium significantly increased the growth of SM-1. It was concluded that the complete genome of SM-1 provided fundamental data for further investigation of its physiology and genetics, in addition to the carbon metabolism revealed in this study.展开更多
基金This paper is dedicated to the late Professor JS Chiao, who initiated the research in China for rifamycin production employing A. mediterranei more than 30 years ago and who continued the endeavor to resolve the mechanism of the 'nitrate stimulating effect' up to the last breath of his life. This work was supported by the National Natural Science Foundation of China (30830002), the National High Technology Research and Development Program of China (2007AA021301, 2007AA021503), and the Research Unit Fund of Li Ka Shing Institute of Health Sciences (7103506).
文摘Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10 236 715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9 228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel 'quasicore' with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.
基金Supported by the Knowledge Innovation Program of Chinese Academy of Sciences (No. KSCX2-YW-G-073)
文摘In this study, the 454 pyrosequencing technology was used to analyze the DNA of the Microcystis aeruginosa symbiosis system from cyanobacterial algal blooms in Taihu Lake, China. We generated 183 228 reads with an average length of 248 bp. Running the 454 assembly algorithm over our sequences yielded 22 239 significant contigs. After excluding the M. aeruginosa sequences, we obtained 1 322 assembled contigs longer than 1 000 bp. Taxonomic analysis indicated that four kingdoms were represented in the community: Archaea (n = 9; 0.01%), Bacteria (n = 98 921; 99.6%), Eukaryota (n = 373; 3.7%), and Viruses (n = 18; 0.02%). The bacterial sequences were predominantly Alphaproteobacteria (n = 41 805; 83.3%), Betaproteobacteria (n = 5 254; 10.5%) and Gammaproteobacteria (n = 1 180; 2.4%). Gene annotations and assignment of COG (clusters of orthologous groups) functional categories indicate that a large number of the predicted genes are involved in metabolic, genetic, and environmental information processes. Our results demonstrate the extraordinary diversity of a microbial community in an ectosymbiotic system and further establish the tremendous utility of pyrosequencing.
基金supported by the project "Transmission Mode of Tuberculosis" (2008ZX100/03-010-02)"Warning Mode of Tuberculosis" (2008ZX10003-008) of the National Key Programme of Mega Infectious Diseasesupported by the project "Mycobacterium tuberculosis genome SNP analysis and research on the origin of the Beijing family strains" (2011SKLID208) of State Key Laboratory for Infectious Disease Prevention and Control
文摘Objective To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. Methods Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC5180) were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. Results The Hunter-Gaston Index (HGI) for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. boris and M. africanum strains from the four loci. Conclusion We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.
基金supported by grants from the National Natural Science Foundation of China 30400191 and 30570797
文摘Objective: To evaluate the effects of polymorphisms in TLR7 and TLRS(as potential candidate genes) on asthma risk and asthma-related phenotypes. Methods: We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results: The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males (adjusted ORs = 0.126, 95% CIs = 0.016-0.995). The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis (adjusted ORs = 0.18, 95% CIs = 0.04-0.90). The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion:TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.
文摘Objective: To investigate the effect of insulin-like growth factor 1 receptor (IGF1R) small interfering RNA (siRNA) on the growth of human liver cancer SMMC7721 cell xenograft in nude mice. Methods: siRNA targeting IGF1R was designed, and plasmid SMMC7721-1GF1R-siRNA was constructed and transfected into SMMC7721 cells (SMMC7721-1GF1R-siRNA cells); the cells transfected with SMMC7721-1GF1 R-mutation (SMMC7721-1GF1 R-mutation cells) were used as negative con- trol, and untransfected cells as empty control. Stable cell clones were screened by G418, and transplanted into nude mice to establish cancer xenograft. Tumor growth was monitored. Tumor morphology was observed with HE staining. The expression of IGF1R protein in tumor tissues was detected by Western blot. Microvessel density (MVD) in tumor tissues was detected by SP immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Results: The tumor volume was significantly smaller in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (P 〈 0.05). Necrosis and cell apoptosis were found in SMMC7721- IGF1R-siRNA group. The expression of IGF1R protein was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (P 〈 0.05). MVD was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (11.3 ± 4.4 vs. 36.7 ± 7.6 and 28.4 ±6.5, P 〈 0.05). The apoptosis rate of tumor cells was significantly higher in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups [(50.2 ± 6.4)% vs. (5.4 ± 1.0)% or (6.0 ±2.1)%, P〈0.05]. Conclusion: IGF1R siRNA can inhibit the growth of SMMC7721 cell xenograft in nude mice.
基金Supported by grants from National Nature Science Foundation of China (30470951) and National Science Foundation for Distinguished YoungScholars of China (39925023).
文摘Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta, COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21- 22 and COLIA2 at 7q22.1. The Linkage ( Version 5. 1 ) was used for 2-point analysis. DNA sequencing was used to screen and identify the mutation. Results A linkage to the markers on chromosome 17q21-22 was observed. Se- quence analysis of COLIA1 revealed a splicing mutation (IVSS-2A 〉 G) that converted the 3' end of intron 8 from AG to GG. Conclusion This mutation ( IVS 8-2A 〉 G) is novel, and has not yet been registered in the Human Type I and Type Ⅲ Collagen Mutations Database.
基金The study was reviewed and approved by the Zhongshan Hospital of Fudan University Institutional Review Board(Approval No.B2018-234).
文摘BACKGROUND The diagnostic and economic value of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale.AIM To reassess the diagnostic and economic value of the three tumor biomarkers.METHODS A retrospective analysis of all 32857 subjects who underwent CEA,CA19-9,CA72-4,gastroscopy and colonoscopy from October 2006 to May 2018 was conducted.Then,we assessed the discrimination and clinical usefulness.Total cost,cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes(gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive).RESULTS The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer(CRC),while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers(GICs).Regarding early diagnosis,only CEA could be used for early CRC.The combination of biomarkers didn’t greatly increase the area under the curve.The economic indicators of CEA were superior to those of CA19-9,CA72-4 and any combination.At the threshold of 1.8μg/L to 10.4μg/L,all four indicators of CEA were lower than those in the scheme that conducted gastrointestinal endoscopy only.Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable.CONCLUSION CEA had qualified diagnostic value for CRC and superior economic value for GICs,especially for elderly health checkup subjects.CA72-4 was not suitable as a diagnostic biomarker.
基金Supported by Grants from the National Natural Science Foundation of China,No.30900745the National High-Tech Research and Development Program(863 Program),No.2012AA020103
文摘Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related death. More than 80% of diagnoses occur at the middle to late stage of the disease, highlighting an urgent need for novel biomarkers detectable at earlier stages. Recently, aberrantly expressed microRNAs (miRNAs) have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis. This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013. Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis, tumor proliferation, distant metastasis and invasion. Furthermore, tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing. As miRNAs in plasma/serum are well protected from RNases, they remain stable under harsh conditions. Thus, potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection. Circulating miRNAs, as well as tissue miRNAs, may allow for the detection of gastric cancer at an early stage, prediction of prognosis, and monitoring of recurrence and/or lymph node metastasis. Taken together, the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
基金The National High Technology Research and Development Program of China 863 Project, No. 2006AA02Z4C5
文摘AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS:One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS:In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels ≥ 104 to < 105; ≥ 105 to < 106; ≥ 106 to < 107; ≥ 107 copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.CONCLUSION:The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 104-107 range.
文摘Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira that infects humans and a wide range of animals. By combining computational prediction and high-accuracy tandem mass spectra, we revised the genome annotation of Leptospira interrogans serovar Lai, a free-living pathogenic spirochete responsible for leptospirosis, providing substantial peptide evidence for novel genes and new gene boundaries. Subsequently, we presented a high-coverage proteome analysis of protein expression and multiple posttranslational modifications (PTMs). Approximately 64.3% of the predicted L. interrogans proteins were cataloged by detecting 2 540 proteins. Meanwhile, a profile of multiple PTMs was concurrently established, containing in total 32 phosphorylated, 46 acetylated and 155 methylated proteins. The PTM systems in the serovar Lai show unique features. Unique eukaryotic-like features of L. interrogans protein modifications were demonstrated in both phosphorylation and arginine methylation. This systematic analysis provides not only comprehensive information of high-coverage protein expression and multiple modifications in prokaryotes but also a view suggesting that the evolutionarily primitive L. interrogans shares significant similarities in protein modification systems with eukaryotes.
文摘The goal of the Human Genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromosome 3 as its share of this historic project, referred as “Beijing Region”. The complete sequence of this region comprises of 17.4 megabasepairs (Mb) with an average GC content of 42% and an average recombination rate of 2.14 cM/Mb. Within Beijing Region, 122 known and 20 novel genes are identified, as well as 42607 single nucleotide polymorphisms (SNPs). Comprehensive analyses also reveal: (i) gene density and GC-content of Beijing Region are in agreement with human cytogenetic maps, i.e. G-minus bands are GC-rich and of a high gene density, whereas G-plus bands are GC-poor and of a relatively low gene density; (ii) the average recombination rate within Beijing Region is rela-tively high compared with other regions of chromosome 3, with the highest recombination rate of 6.06 cM/Mb in the subtelomeric area; (iii) it is most likely that a large gene, associated with the mammary gland, may reside in the 1.1 Mb gene-poor area near the telomere; (iv) many dis-ease-related genes are genetically mapped to Beijing Region, including those associated with cancers and metabolic syndromes. All make Beijing Region an important target for in-depth mo-lecular investigations with a purpose of medical applications.
文摘The amino acid biosynthesis and proteolytic system of Lactobacillus bulgaricus (L.Bulgaricus ) is important for its growth in niche-specific environments, as well as for flavour formation in the food industry. Comparative analyses of 4 completed sequences of the L.Bulgaricus strain genome on a genomic scale revealed that genes involved in amino acids synthesis were undergoing reductive evolution. However, the selected industrial strains, namely, L.Bulgaricus 2038 and L.Bulgaricus ND02, retained more complete genes in the amino acid synthesis and proteolytic system category than the laboratory strains, and have some unique genes and pathways for obtaining amino acids that enable these bacteria to adapt to their various environmental niches.
文摘BACKGROUND: Studies have shown that adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene influences atherosclerosis. Studies have also demonstrated that cerebral infarction does not occur often in pre-menopausal women. It has been, therefore, assumed that sex plays a role in R219K polymorphism of ABCA1 gene and cerebral infarction. OBJECTIVE: To explore the relationship between lipid metabolism-correlated R219K polymorphism of ABCA1 gene, risk factors of cerebral infarction and lipid level, and to determine whether there were significant differences in gender between R219K polymorphism of ABCA1 gene and cerebral infarction. DESIGN, TIME AND SETTING: A multicentral and non-randomized, controlled study based on gene polymorphism was performed at the Chinese National Human Genome Center, and lipid concentrations were measured at Beijing Xuanwu Hospital. Patients with cerebral infarction and healthy subjects were enrolled from eight hospitals of six provinces of China between October 2002 and December 2004. PARTICIPANTS: There were 177 patients in the cerebral infarction group, including 119 males and 58 females, with a mean age of (60 -+ 13) years, and 234 healthy subjects in the normal control group, including 79 males and 155 females, with a mean age of (58 ± 12) years. METHODS: R219K polymorphism of the ABCA1 gene was detected using polymerase chain reaction-restriction fragment length polymorphism, and blood lipid concentrations were simultaneously measured. MAIN OUTCOME MEASURES: Genotype and allele frequency of R219K polymorphic site, and blood lipid concentrations. RESULTS: RR genotype and R allele frequency of males in the cerebral infarction were significantly greater than males in the normal control group [RR genotype: x2 = 5.305, OR (95% CO, 2.326 (1.120 4.828), P〈 0.05; R allele: x2= 4.219, OR (95% CO, 1.528 (1.019 2.292), P〈 0.05]. In addition, RR genotype and R allele frequency of males were significantly greater than females in the cerebral infarction group [RR genotype: x2= 5.172, OR (95% C/), 2.604 (1.120-6.057), P〈 0.05; R allele: x2= 4.818, OR (95% CO, 1.652 (1.053 2.589), P〈 0.05]. There were no significant differences between genotype and lipid concentrations between the two groups (P〉 0.05). CONCLUSION: The RR genotype of ABCA1 R219K might be associated with onset of cerebral infarction in males, but blood lipid concentrations do not relate to R219K polymorphism.
基金supported by the National Key Research Program of China 2016YFC1302601。
文摘Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.Methods The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.Results Black males were diagnosed at a later stage, more commonly with local or distant metastases.The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival(OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.Conclusion Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.
文摘Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemi- sinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on compre- hensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the chal- lenge of increasing global demand of artemisinin.
文摘We conducted a genome-wide scan, in which 358 well distributed fluorescent dye-labeled microsatellite marker sets were applied in 32 Chinese Han type 2 diabetes families from Northern China to search for the susceptibility gene loci. The data collected from screening all the chromosomes of genome were genotyped by using genescan and genotyping software, then, parametric and non-parametric multipoint test, and affected sib-pair analysis as well, were used to analyze the data. We identified some susceptibility gene loci residing in chromosomes 1,12,18,20, respectively, or precisely, located around D1S214, D1S207, D1S218, D1S235, D12S336, D18S61 and D20S118. The comparison of this result with those from other regions and races reflected the complexity and heterogeneity of type 2 diabetes.
文摘Ketogulonigenium sp. may convert L-sorbose into 2-keto-L-gulonic acid, the vitamin C precursor. The genome of Ketogulonigenium sp. WB0104 consists of a circular 2765030 bp chromo- some with 61.69% G+C content and two circular plasmids of 267968 and 242707 bp. The genome contains 2727 open reading frames (ORFs). The systems of replication, transcription, translation, carbohydrate and energy metabolism are intact, but the repair system is incomplete. About 640 predicted ORFs have been found to encode transporter pro- teins, which account for about one fourth of total predicted ORFs, noticeably higher than other docu- mented bacteria. This may be due to the fact that WB0104 adapts to soil circumstance.
基金supported by the National Science Foundation of China(No.30870039)the National Basic Research Program of China(973 Program,No.2010CB630903)
文摘Acidithiobacillus caldus is one of the dominant sulfur-oxidizing bacteria in bioleaching reactors. It plays the essential role in maintaining the high acidity and oxidation of reduced inorganic sulfur compounds during bioleaching process. In this report, the complete genome sequence of A. caldus SM-1 is presented. The genome is composed of one chromosome (2,932,225 bp) and four plasmids (pLAtcl, pLAtc2, pLAtc3, pLAtcm) and it is rich in repetitive sequences (accounting for 11% of the total genome), which are often associated with transposable genetic elements. In particular, twelve copies of ISAtfe and thirty-seven copies of ISAtcl have been identified, suggesting that they are active transposons in the genome. A. caldus SM-1 encodes all enzymes for the central metabolism and the assimilation of carbon compounds, among which 29 proteins/enzymes were identifiable with proteomic tools. The SM-1 fixes CO2 via the classical Calvin-Bassham--Benson (CBB) cycle, and can operate complete Embden-Meyerhof pathway (EMP), pentose phosphate pathway (PPP), and gluconeogenesis. It has an incomplete tricarboxylic acid cycle (TCA). Four putative transporters involved in carbohydrate uptake were identified. Taken together, the results suggested that SM-1 was able to assimilate carbohydrates and this was subsequently confirmed experimentally because addition of 1% glucose or sucrose in basic salt medium significantly increased the growth of SM-1. It was concluded that the complete genome of SM-1 provided fundamental data for further investigation of its physiology and genetics, in addition to the carbon metabolism revealed in this study.