Difference in the genomic compositions of prokaryotes is the basis of the diversity in their biological characters. However, besides their flora-or strain-specific genes,those floras with closer relationship in the ev...Difference in the genomic compositions of prokaryotes is the basis of the diversity in their biological characters. However, besides their flora-or strain-specific genes,those floras with closer relationship in the evolution also have conserved “backbone sequences”, which reveal the marks of their origin and evolution, and these “backbone sequences”are just the basis of their elementary living abilities and common biological properties. Shigella is very closely related to E. coli in the origin and evolution, and may turn out to belong to the same genus. In this study, a microarray containing E. coli K-12 whole genome and Sf301 specific ORFs is used to investigate the genomic components of four Shigella strains. The results indicate that 16%-22% K-12 ORFs sequences are not detected in the genome of Shigella strains while the genome of Shigella contains at least 2800 conserved ORFs, which compose the common “backbone sequences”.Advanced analysis indicated that the “backbone sequences”are the essential components in maintaining the normal physiological activities of intestinal bacteria. Furthermore,only 20% Sf301-specific ORFs exist in other strains simultaneously, which demonstrate the great genome heterogeneity and the genetic diversity among the strains.展开更多
Comparative genome analysis is performed between Shigella flexneri 2a strain 301 and its close relatives, the nonpathogenic E. Coli K-12 strain MG1655. Result shows that there are 136 DNA segments whose size is larger...Comparative genome analysis is performed between Shigella flexneri 2a strain 301 and its close relatives, the nonpathogenic E. Coli K-12 strain MG1655. Result shows that there are 136 DNA segments whose size is larger than 1000 bp absent from Shigella flexneri 2a strain 301, which is up to 717253 bp in total length. These deleted segments altogether contain 670 open reading frames (ORFs). Prediction of these ORFs indicates that there are 40% genes of unknown function. The other genes of definite functions encode metabolic enzymes, structure proteins, transcription regulatory factors and some elements correlated with horizontal transfer. Here we compare the complete genomic sequences of the two closely related species, which differ in pathogenic phenotype. To our knowledge, this not only reveals the difference of genomic sequence between the two important enteric pathogens for the first time, but also provides valuable clues to further researches in its process of physiological activity, pathogenesis and the evolution of enteric bacteria.展开更多
Human tumor necrosis factor α (hTNFα), a pleiotropic cytokine withactivities ranging from host defense mechanisms in infection and injury to severe toxicity in septicshock or other related diseases, is a promising t...Human tumor necrosis factor α (hTNFα), a pleiotropic cytokine withactivities ranging from host defense mechanisms in infection and injury to severe toxicity in septicshock or other related diseases, is a promising target for drug screening. Using the SELEX(systematic evolution of ligands by exponential enrichment) process, we isolated oligonucleotideligands (aptamers) with high affinities for hTNFα. Aptamers were selected from a starting pool of40 randomized sequences composed of about 10^(15) RNA molecules. Representative aptamers weretruncated to the minimal length with high affinity for hTNFα and were further modified byreplacement of 2'-OH with 2'-F and 2'-NH_2 at all ribopurine positions. These modified RNA aptamerswere resistant to nuclease. The specificity of these aptamers for hTNFα was confirmed, and theiractivity to inhibit the cytotoxicity of hTNFα on mouse L929 cells was determined. Resultsdemonstrated that four 2'-NH_2-modified aptamers bound to hTNFα with high affinity and blocked thebinding of hTNFα to its receptor, thus protecting the L929 cells from the cytotoxicity of hTNFα.Oligonucleotide aptamers described here are potential therapeutics and diagnostics forhTNFα-related diseases.展开更多
文摘Difference in the genomic compositions of prokaryotes is the basis of the diversity in their biological characters. However, besides their flora-or strain-specific genes,those floras with closer relationship in the evolution also have conserved “backbone sequences”, which reveal the marks of their origin and evolution, and these “backbone sequences”are just the basis of their elementary living abilities and common biological properties. Shigella is very closely related to E. coli in the origin and evolution, and may turn out to belong to the same genus. In this study, a microarray containing E. coli K-12 whole genome and Sf301 specific ORFs is used to investigate the genomic components of four Shigella strains. The results indicate that 16%-22% K-12 ORFs sequences are not detected in the genome of Shigella strains while the genome of Shigella contains at least 2800 conserved ORFs, which compose the common “backbone sequences”.Advanced analysis indicated that the “backbone sequences”are the essential components in maintaining the normal physiological activities of intestinal bacteria. Furthermore,only 20% Sf301-specific ORFs exist in other strains simultaneously, which demonstrate the great genome heterogeneity and the genetic diversity among the strains.
基金supported by the State“973”Key Basic Research Program(Grant No.G1999054103)the State“863”High-Tech Project(Grant No.Z19-02-05-01)+1 种基金Beijing Innovation Engineering(Grant No.955020700)the North China Pharmaceutical Corporation(NCPC)
文摘Comparative genome analysis is performed between Shigella flexneri 2a strain 301 and its close relatives, the nonpathogenic E. Coli K-12 strain MG1655. Result shows that there are 136 DNA segments whose size is larger than 1000 bp absent from Shigella flexneri 2a strain 301, which is up to 717253 bp in total length. These deleted segments altogether contain 670 open reading frames (ORFs). Prediction of these ORFs indicates that there are 40% genes of unknown function. The other genes of definite functions encode metabolic enzymes, structure proteins, transcription regulatory factors and some elements correlated with horizontal transfer. Here we compare the complete genomic sequences of the two closely related species, which differ in pathogenic phenotype. To our knowledge, this not only reveals the difference of genomic sequence between the two important enteric pathogens for the first time, but also provides valuable clues to further researches in its process of physiological activity, pathogenesis and the evolution of enteric bacteria.
文摘Human tumor necrosis factor α (hTNFα), a pleiotropic cytokine withactivities ranging from host defense mechanisms in infection and injury to severe toxicity in septicshock or other related diseases, is a promising target for drug screening. Using the SELEX(systematic evolution of ligands by exponential enrichment) process, we isolated oligonucleotideligands (aptamers) with high affinities for hTNFα. Aptamers were selected from a starting pool of40 randomized sequences composed of about 10^(15) RNA molecules. Representative aptamers weretruncated to the minimal length with high affinity for hTNFα and were further modified byreplacement of 2'-OH with 2'-F and 2'-NH_2 at all ribopurine positions. These modified RNA aptamerswere resistant to nuclease. The specificity of these aptamers for hTNFα was confirmed, and theiractivity to inhibit the cytotoxicity of hTNFα on mouse L929 cells was determined. Resultsdemonstrated that four 2'-NH_2-modified aptamers bound to hTNFα with high affinity and blocked thebinding of hTNFα to its receptor, thus protecting the L929 cells from the cytotoxicity of hTNFα.Oligonucleotide aptamers described here are potential therapeutics and diagnostics forhTNFα-related diseases.
