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11.
Nierman WC Eisen JA Fleischmann RD Fraser CM 《Current opinion in structural biology》2000,10(3):343-348
Genome sequence information has continued to accumulate at a spectacular pace during the past year. Details of the sequence and gene content of human chromosome 22 were published. The sequencing and annotation of the first two Arabidopsis thaliana chromosomes was completed. The sequence of chromosome 3 from Plasmodium falciparum, the second sequenced malaria chromosome, was reported, as was that of chromosome 1 from Leishmania major. The complete genomic sequences of five microbes were reported. Approaches to using data from completely sequenced microbial genomes in phylogenetic studies are being explored, as is the application of microarrays to whole genome expression analysis. 相似文献
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John J. Varga Liliana Losada Adrian M. Zelazny Lauren Brinkac Derek Harkins Diana Radune Jessica Hostetler Elizabeth P. Sampaio Catherine M. Ronning William C. Nierman David E. Greenberg Steven M. Holland Joanna B. Goldberg 《Journal of bacteriology》2012,194(22):6356-6357
Burkholderia multivorans is a Gram-negative bacterium and a member of the Burkholderia cepacia complex, which is frequently associated with respiratory infections in people with cystic fibrosis (CF) and chronic granulomatous disease (CGD). We are reporting the genome sequences of 4 B. multivorans strains, 2 from CF patients and 2 from CGD patients. 相似文献
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Schutzer SE Schlater LR Ronning CM DeShazer D Luft BJ Dunn JJ Ravel J Fraser-Liggett CM Nierman WC 《PloS one》2008,3(4):e2058
Background
Burkholderia mallei is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens.Methodology/Principal Findings
We performed WGS on a strain of B. mallei, SAVP1, previously pathogenic, that was experimentally infected in 6 equids (4 ponies, 1 mule, 1 donkey), natural hosts, for purposes of producing antibodies. Multiple high inocula were used in some cases. Unexpectedly SAVP1 appeared to be avirulent in the ponies and mule, and attenuated in the donkey, but induced antibodies. We determined the genome sequence of SAVP1 and compared it to a strain that was virulent in horses and a human. In comparison, this phenotypic avirulent SAVP1 strain was missing multiple genes including all the animal type III secretory system (T3SS) complex of genes demonstrated to be essential for virulence in mice and hamster models. The loss of these genes in the SAVP1 strain appears to be the consequence of a multiple gene deletion across insertion sequence (IS) elements in the B. mallei genome. Therefore, the strain by itself is unlikely to revert naturally to its virulent phenotype. There were other genes present in one strain and not the other and vice-versa.Conclusion/Significance
The discovery that this strain of B. mallei was both avirulent in the natural host ponies, and did not possess T3SS associated genes may be fortuitous to advance biodefense research. The deleted virulence-essential T3SS is not likely to be re-acquired naturally. These findings may provide a basis for exclusion of SAVP1 from the Select Agent regulation or at least discussion of what else would be required for exclusion. This exclusion could accelerate research by investigators not possessing BSL-3 facilities and facilitate the production of reagents such as antibodies without the restraints of Select Agent regulation. 相似文献15.
The role of nitric oxide in cancer 总被引:4,自引:0,他引:4
WEIMING XU Li ZHI LIU MARILENA LOIZIDOU MOHAMED AHMED IAN G CHARLES Wolfson Institute for Biomedical Research Cruciform Building Gower Street UCL London WC E AUUK Department of Surgery Charles Bell House - Riding House Street UCL London WW EJ UK 《Cell research》2002,(Z2)
Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including va-sodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases (NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interestingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting the etiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and has been associated with tumour grade, proliferation rate and expression of important signaling components associated with cancer development such as the oestrogen receptor. It appears that high levels of NOS expression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumor cells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxically therefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic pro 相似文献
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van den Berg MA Albang R Albermann K Badger JH Daran JM Driessen AJ Garcia-Estrada C Fedorova ND Harris DM Heijne WH Joardar V Kiel JA Kovalchuk A Martín JF Nierman WC Nijland JG Pronk JT Roubos JA van der Klei IJ van Peij NN Veenhuis M von Döhren H Wagner C Wortman J Bovenberg RA 《Nature biotechnology》2008,26(10):1161-1168
18.
Bhabhra R Richie DL Kim HS Nierman WC Fortwendel J Aris JP Rhodes JC Askew DS 《Eukaryotic cell》2008,7(4):575-583
Aspergillus fumigatus is an important opportunistic fungal pathogen that is responsible for high mortality rates in the immunosuppressed population. CgrA, the A. fumigatus ortholog of a Saccharomyces cerevisiae nucleolar protein involved in ribosome biogenesis, contributes to the virulence of this fungus by supporting rapid growth at 37 degrees C. To determine how CgrA affects ribosome biogenesis in A. fumigatus, polysome profile and ribosomal subunit analyses were performed on both wild-type A. fumigatus and a DeltacgrA mutant. The loss of CgrA was associated with a reduction in the level of 80S monosomes as well as an imbalance in the 60S:40S subunit ratio and the appearance of half-mer ribosomes. The gene expression profile in the DeltacgrA mutant revealed increased abundance of a subset of translational machinery mRNAs relative to the wild type, suggesting a potential compensatory response to CgrA deficiency. Although DeltacgrA conidia germinated normally at 22 degrees C, they swelled excessively when incubated at 37 degrees C and accumulated abnormally high numbers of nuclei. This hypernucleated phenotype could be replicated pharmacologically by germinating wild-type conidia under conditions of reductive stress. These findings indicate that the germination process is particularly vulnerable to global disruption of protein synthesis and suggest that CgrA is involved in both ribosome biogenesis and polarized cell growth in A. fumigatus. 相似文献
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Han Song Junghyun Hwang Jaehee Myung Hyoseok Seo Hyojeong Yi Hee-Sun Sim Bong-Su Kim William C. Nierman Heenam Stanley Kim 《Molecules and cells》2009,27(2):237-241
Pathogens Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) contain a large number (> 12,000) of Simple Sequence Repeats (SSRs). To study the extent to which these features have
contributed to the diversification of genes, we have conducted comparative studies with nineteen genomes of these bacteria.
We found 210 genes with characteristic types of SSR variations. SSRs with nonamer repeat units were the most abundant, followed
by hexamers and trimers. Amino acids with smaller and nonpolar R-groups are preferred to be encoded by the variant SSRs, perhaps
due to their minimal impacts to protein functionality. A majority of these genes appears to code for surface or secreted proteins
that may directly interact with the host factors during pathogenesis or other environmental factors. There also are others
that encode diverse functions in the cytoplasm, and this protein variability may reflect an extensive involvement of phase
variation in survival and adaptation of these pathogens. 相似文献