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61.
Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals 总被引:23,自引:0,他引:23 下载免费PDF全文
Maines TR Lu XH Erb SM Edwards L Guarner J Greer PW Nguyen DC Szretter KJ Chen LM Thawatsupha P Chittaganpitch M Waicharoen S Nguyen DT Nguyen T Nguyen HH Kim JH Hoang LT Kang C Phuong LS Lim W Zaki S Donis RO Cox NJ Katz JM Tumpey TM 《Journal of virology》2005,79(18):11788-11800
The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret. 相似文献
62.
Two plasmid DNA constructs were obtained by cloning separately into the eukaryotic expression vector pcDNA3.1/V5-His-TOPO the wall-associated protein A (wapA) gene of Streptococcus mutans GS-5 or its truncated derivative antigen A (agA) gene encoding a known candidate antigen for dental caries vaccine. The immunogenicity of the two constructs, designated pcDNA-wapA and pcDNA-agA, was compared by intranasal immunization of two groups of mice using the cationic DMRIE-C (1,2-dimyristyloxypropyl-3-dimethylhydroxy ethyl ammonium bromide-cholesterol) as an adjuvant. Immunization with pcDNA-wapA or pcDNA- agA resulted in specific salivary IgA and systemic IgG antibodies to the target antigens after two doses given at 3-week intervals. Higher salivary IgA level was observed in the mice immunized with the pcDNA-wapA vaccine compared to those immunized with the pcDNA-agA vaccine. Furthermore, anti-WapA antibody inhibited S. mutans sucrose-dependent adherence suggesting a potential protection against S. mutans colonization of the tooth, while anti-AgA had no significant effect. Indeed, prediction and analysis of protein epitopes showed that WapA contains highly promiscuous MHC-II binding motifs in addition to those found in AgA. Immunodot assay confirmed that WapA bound biotin-labeled dextran, whereas AgA did not. These data indicated that full-length WapA is a better candidate vaccine antigen than the soluble AgA, which is truncated in the hydrophobic membrane and wall-spanning region. 相似文献
63.
Temporal Changes between Ecological Regimes in a Range of Primary and Secondary Salinised Wetlands 总被引:4,自引:4,他引:0
Karin?Strehlow Jenny?DavisEmail author Lien?Sim Jane?Chambers Stuart?Halse David?Hamilton Pierre?Horwitz Arthur?McComb Ray?Froend 《Hydrobiologia》2005,552(1):17-31
Many rivers and wetlands in south-western Australia are threatened by salinisation due to rising saline watertables, which
have resulted from land clearing and the replacement of deep-rooted perennial species with shallow-rooted annual species.
A four to six weekly sampling program of water quality, submerged macrophytes and macroinvertebrates was undertaken at six
wetlands, from September 2002 to February 2004, to investigate seasonal variation in a range of primary and secondary saline
systems. The wetlands dried and filled at different times in response to local rainfall patterns, and salinities varied accordingly
with evapoconcentration and dilution. Two types of clear-water wetlands were recognised; those dominated by submerged aquatic
macrophytes (Ruppia, Lepilaena and Lamprothamnium) and those dominated by benthic microbial communities. Two types of turbid wetlands were also recognised; those with high
concentrations of phytoplankton and those with high concentrations of suspended sediments. A primary saline lake and two lakes
that have only recently been affected by secondary salinisation persisted in a clear, macrophyte-dominated regime throughout
most of the study period, except during drying and filling. Two lakes with a long history of secondary salinisation (70 years)
moved between regimes over the study period. A clear, benthic microbial community – dominated regime only persisted at the
wetland which contained permanent water throughout the study period. The turbid regimes were only present during drying and
refilling phases. A richer and more abundant macroinvertebrate fauna was associated with the clear, macrophyte- dominated
wetlands. Our results suggest that the development of management guidelines that recognise the presence of different ecological
regimes and that consider the interactions between water regime, salinity, and primary and secondary production will be more
useful in protecting biodiversity and ecological function in these systems than managing salinity as a single factor. 相似文献
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Gene expression analysis of zebrafish heart regeneration 总被引:1,自引:0,他引:1
69.
Brian J. Hawkins Krishna M. Irrinki Karthik Mallilankaraman Yu-Chin Lien Youjun Wang Cunnigaiper D. Bhanumathy Ramasamy Subbiah Michael F. Ritchie Jonathan Soboloff Yoshihiro Baba Tomohiro Kurosaki Suresh K. Joseph Donald L. Gill Muniswamy Madesh 《The Journal of cell biology》2010,190(3):391-405
Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca2+ signaling. However, precisely how oxidants influence Ca2+ signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca2+ mobilization from an oscillatory to a sustained elevated pattern via calcium release–activated calcium (CRAC)–mediated capacitive Ca2+ entry, and stromal interaction molecule 1 (STIM1)– and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca2+ entry alters mitochondrial Ca2+ handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to oxidant stress and evokes constitutive Ca2+ entry independent of intracellular Ca2+ stores. These experiments reveal that cysteine 56 is a sensor for oxidant-dependent activation of STIM1 and demonstrate a molecular link between oxidant stress and Ca2+ signaling via the CRAC channel. 相似文献
70.
Chin-Yuan Chang Yin-Cheng Hsieh Ting-Yi Wang Yi-Chin Chen Yu-Kuo Wang Ting-Wei Chiang Yi-Ju Chen Cheng-Hsiang Chang Chun-Jung Chen Tung-Kung Wu 《The Journal of biological chemistry》2010,285(50):39500-39510
Aminoacylhistidine dipeptidases (PepD, EC 3.4.13.3) belong to the family of M20 metallopeptidases from the metallopeptidase H clan that catalyze a broad range of dipeptide and tripeptide substrates, including l-carnosine and l-homocarnosine. Homocarnosine has been suggested as a precursor for the neurotransmitter γ-aminobutyric acid (GABA) and may mediate the antiseizure effects of GABAergic therapies. Here, we report the crystal structure of PepD from Vibrio alginolyticus and the results of mutational analysis of substrate-binding residues in the C-terminal as well as substrate specificity of the PepD catalytic domain-alone truncated protein PepDCAT. The structure of PepD was found to exist as a homodimer, in which each monomer comprises a catalytic domain containing two zinc ions at the active site center for its hydrolytic function and a lid domain utilizing hydrogen bonds between helices to form the dimer interface. Although the PepD is structurally similar to PepV, which exists as a monomer, putative substrate-binding residues reside in different topological regions of the polypeptide chain. In addition, the lid domain of the PepD contains an “extra” domain not observed in related M20 family metallopeptidases with a dimeric structure. Mutational assays confirmed both the putative di-zinc allocations and the architecture of substrate recognition. In addition, the catalytic domain-alone truncated PepDCAT exhibited substrate specificity to l-homocarnosine compared with that of the wild-type PepD, indicating a potential value in applications of PepDCAT for GABAergic therapies or neuroprotection. 相似文献