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91.
92.
Schmolke M Manicassamy B Pena L Sutton T Hai R Varga ZT Hale BG Steel J Pérez DR García-Sastre A 《PLoS pathogens》2011,7(8):e1002186
Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20(th) century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism. 相似文献
93.
Background
We previously showed that equivalence between two identified zebrafish motoneurons is broken by interactions with identified muscle fibers that act as an intermediate target for the axons of these motoneurons. Here we investigate the molecular basis of the signaling interaction between the intermediate target and the motoneurons.Principal Findings
We provide evidence that Netrin 1a is an intermediate target-derived signal that causes two equivalent motoneurons to adopt distinct fates. We show that although these two motoneurons express the same Netrin receptors, their axons respond differently to Netrin 1a encountered at the intermediate target. Furthermore, we demonstrate that when Netrin 1a is knocked down, more distal intermediate targets that express other Netrins can also function to break equivalence between these motoneurons.Significance
Our results suggest a new role for intermediate targets in breaking neuronal equivalence. The data we present reveal that signals encountered during axon pathfinding can cause equivalent neurons to adopt distinct fates. Such signals may be key in diversifying a neuronal population and leading to correct circuit formation. 相似文献94.
Kawaguchi S Kurihara H King R Hale L Berli T Robinson JP Ishida A Wakita M Virtue P Nicol S Ishimatsu A 《Biology letters》2011,7(2):288-291
Antarctic krill embryos and larvae were experimentally exposed to 380 (control), 1000 and 2000 µatm pCO2 in order to assess the possible impact of ocean acidification on early development of krill. No significant effects were detected on embryonic development or larval behaviour at 1000 µatm pCO2; however, at 2000 µatm pCO2 development was disrupted before gastrulation in 90 per cent of embryos, and no larvae hatched successfully. Our model projections demonstrated that Southern Ocean sea water pCO2 could rise up to 1400 µatm in krill''s depth range under the IPCC IS92a scenario by the year 2100 (atmospheric pCO2 788 µatm). These results point out the urgent need for understanding the pCO2-response relationship for krill developmental and later stages, in order to predict the possible fate of this key species in the Southern Ocean. 相似文献
95.
Anthocyanins facilitate tungsten accumulation in Brassica 总被引:1,自引:0,他引:1
Kerry L. Hale Hale A. Tufan Ingrid J. Pickering Graham N. George Norman Terry Marinus Pilon Elizabeth A. H. Pilon-Smits 《Physiologia plantarum》2002,116(3):351-358
Accumulation of molybdenum in Brassica was recently found to be correlated with anthocyanin content, involving the formation of a blue complex. Here the role of anthocyanins in tungsten sequestration was investigated using three species of Brassica : B. rapa (cv. Fast plants), B. juncea (Indian mustard) and B. oleracea (red cabbage). Seedlings of B. rapa and B. juncea turned blue when supplied with colourless tungstate. The blue compound co-localized with anthocyanins in the peripheral cell layers, and the degree of blueness was correlated with anthocyanin content. The direct involvement of anthocyanins in the blue coloration was evident when purified anthocyanins showed a colour change from pink to blue in vitro upon addition of tungstate, over a wide pH range. Anthocyanin production was upregulated 3-fold by W in B. juncea , possibly reflecting a function for anthocyanins in W tolerance or sequestration. The presence of anthocyanins facilitated W accumulation in B. rapa : anthocyanin-containing seedlings accumulated 3-fold more W than an anthocyaninless mutant. There was no correlation between anthocyanin content and W tolerance under these conditions. The nature of the interaction between anthocyanins and tungstate was investigated. X-ray absorption spectroscopy showed no change in the local chemical environment of W upon uptake of tungstate by the plant; HPLC analysis of purified anthocyanin with or without tungstate showed no peak shift after metal treatment. 相似文献
96.
During posthatching development the fins of fishes undergo striking changes in both structure and function. In this article we examine the development of the pectoral fins from larval through adult life history stages in the zebrafish (Danio rerio), describing in detail their pectoral muscle morphology. We explore the development of muscle structure as a way to interpret the fins' role in locomotion. Genetic approaches in the zebrafish model are providing new tools for examining fin development and we take advantage of transgenic lines in which fluorescent protein is expressed in specific tissues to perform detailed three-dimensional, in vivo fin imaging. The fin musculature of larval zebrafish is organized into two thin sheets of fibers, an abductor and adductor, one on each side of an endoskeletal disk. Through the juvenile stage the number of muscle fibers increases and muscle sheets cleave into distinct muscle subdivisions as fibers orient to the developing fin skeleton. By the end of the juvenile period the pectoral girdle and fin muscles have reoriented to take on the adult organization. We find that this change in morphology is associated with a switch of fin function from activity during axial locomotion in larvae to use in swim initiation and maneuvering in adults. The examination of pectoral fins of the zebrafish highlights the yet to be explored diversity of fin structure and function in subadult developmental stages. J. Morphol. (c) 2005 Wiley-Liss, Inc. 相似文献
97.
Gutierrez JA Dorocke JA Knierman MD Gelfanova V Higgs RE Koh NL Hale JE 《BioTechniques》2005,(Z1):13-17
A method is described for the quantitative determination of peptides using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Known limitations imposed by crystal heterogeneity, peptide ionization differences, data handling, and protein quantification with MALDI-TOF mass spectrometry are addressed in this method with a "seed crystal" protocol for analyte-matrix formation, the use of internal protein standards, and a software package called maldi_quant. The seed crystal protocol, a new variation of the fast-evaporation method, minimizes crystal heterogeneity and allows for consistent collection of protein spectra. The software maldi_quant permits rapid and automated analysis of peak intensity data, normalization of peak intensities to internal standards, and peak intensity deconvolution and estimation for vicinal peaks. Using insulin proteins in a background of other unrelated peptides, this method shows an overall coefficient of variance of 4.4%, and a quantitative working range of 0.58-37.5 ng bovine insulin per spot. Coupling of this methodology to powerful analytical procedures such as immunoprecipitation is likely to lead to the rapid and reliable quantification of biologically relevant proteins and their closely related variants. 相似文献
98.
Hale JD Ting YT Jack RW Tagg JR Heng NC 《Applied and environmental microbiology》2005,71(11):7613-7617
Streptococcus mutans UA159, the genome sequence reference strain, exhibits nonlantibiotic mutacin activity. In this study, bioinformatic and mutational analyses were employed to demonstrate that the antimicrobial repertoire of strain UA159 includes mutacin IV (specified by the nlm locus) and a newly identified bacteriocin, mutacin V (encoded by SMU.1914c). 相似文献
99.
Mathews I Schwarzenbacher R McMullan D Abdubek P Ambing E Axelrod H Biorac T Canaves JM Chiu HJ Deacon AM DiDonato M Elsliger MA Godzik A Grittini C Grzechnik SK Hale J Hampton E Han GW Haugen J Hornsby M Jaroszewski L Klock HE Koesema E Kreusch A Kuhn P Lesley SA Levin I Miller MD Moy K Nigoghossian E Ouyang J Paulsen J Quijano K Reyes R Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2005,59(4):869-874
100.
Rife C Schwarzenbacher R McMullan D Abdubek P Ambing E Axelrod H Biorac T Canaves JM Chiu HJ Deacon AM DiDonato M Elsliger MA Godzik A Grittini C Grzechnik SK Hale J Hampton E Han GW Haugen J Hornsby M Jaroszewski L Klock HE Koesema E Kreusch A Kuhn P Lesley SA Miller MD Moy K Nigoghossian E Paulsen J Quijano K Reyes R Sims E Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2005,61(2):444-448