排序方式: 共有169条查询结果,搜索用时 796 毫秒
51.
While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3' and 5' ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6-36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses. 相似文献
52.
Colin Southwell John McKinlay Matt Low David Wilson Kym Newbery Jan L. Lieser Louise Emmerson 《Polar Biology》2013,36(6):843-856
Land-breeding marine animals such as penguins, flying seabirds and pinnipeds are important components of marine ecosystems, and their abundance has been used extensively as an indication of ecosystem status and change. Until recently, many efforts to measure and monitor abundance of these species’ groups have focussed on smaller populations and spatial scales, and efforts to account for perception bias and availability bias have been variable and often ad hoc. We describe a suite of new methods, technologies and estimation procedures for cost-effective, large-scale abundance estimation within a general estimation framework and illustrate their application on large Adélie penguin populations in two regions of East Antarctica. The methods include photographic sample counts, automated cameras for collecting availability data, and bootstrap estimation to adjust counts for the sampling fraction, perception bias, and availability bias, and are applicable for a range of land-breeding marine species. The methods will improve our ability to obtain population data over large spatial and population scales within tight logistic, environmental and time constraints. This first application of the methods has given new insights into the biases and uncertainties in abundance estimation for penguins and other land-breeding marine species. We provide guidelines for applying the methods in future surveys. 相似文献
53.
Matthew N. Henry Michael A. MacDonald Camila A. Orellana Peter P. Gray Marianne Gillard Kym Baker Lars K. Nielsen Esteban Marcellin Stephen Mahler Verónica S. Martínez 《Biotechnology and bioengineering》2020,117(4):1187-1203
Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by-products, and mechanical shear, hindering production. Genetic engineering strategies to reduce apoptosis in CHO cells have been investigated with mixed results. In this review, a contemporary understanding of the real complexity of apoptotic mechanisms and signaling pathways is described; followed by an overview of antiapoptotic cell line engineering strategies tested so far in CHO cells. 相似文献
54.
John J. Vincent Yun Huang Pao-Yang Chen Suhua Feng Joseph H. Calvopiña Kevin Nee Serena A. Lee Thuc Le Alexander J. Yoon Kym Faull Guoping Fan Anjana Rao Steven E. Jacobsen Matteo Pellegrini Amander T. Clark 《Cell Stem Cell》2013,12(4):470-478
- Download : Download high-res image (112KB)
- Download : Download full-size image
55.
Previous mammalian studies have demonstrated that varying levels of signaller arousal are frequently expressed through vocal behaviour. The potential for callers to convey their motivational state may ensure that recipient responses are appropriate to their needs. The current study investigated the influence of behavioural context on Weddell seal mother-pup vocalisation. Mother and pup call rates were calculated within five and seven behavioural contexts, respectively, and the acoustic characteristics of 69 pup calls were measured within four contexts (total calls = 276). Context significantly influenced the temporal patterning of calls, with reuniting mothers and pups and lone active pups emitting more calls than during mother-pup contact periods. Reuniting and lone pup calls were also characterised by longer durations, higher fundamental frequencies, and increased energy in upper harmonics. Results suggest that reunion events and lone pup searching are characterised by calls reflective of heightened arousal, compared with mother-pup contact periods. 相似文献
56.
Iyengar RR Lynch JK Mulhern MM Judd AS Freeman JC Gao J Souers AJ Zhao G Wodka D Doug Falls H Brodjian S Dayton BD Reilly RM Swanson S Su Z Martin RL Leitza ST Houseman KA Diaz G Collins CA Sham HL Kym PR 《Bioorganic & medicinal chemistry letters》2007,17(4):874-878
The optimization of potent MCHr1 antagonist 1 with respect to improving its in vitro profile by replacement of the 3,4-methylenedioxy phenyl (piperonyl) moiety led to the discovery of 19, a compound that showed excellent MCHr1 binding and functional potencies in addition to possessing superior hERG separation, CYP3A4 profile, and receptor cross-reactivity profiles. 相似文献
57.
Gibson WT Hood RL Zhan SH Bulman DE Fejes AP Moore R Mungall AJ Eydoux P Babul-Hirji R An J Marra MA;FORGE Canada Consortium Chitayat D Boycott KM Weaver DD Jones SJ 《American journal of human genetics》2012,90(1):110-118
We used trio-based whole-exome sequencing to analyze two families affected by Weaver syndrome, including one of the original families reported in 1974. Filtering of rare variants in the affected probands against the parental variants identified two different de novo mutations in the enhancer of zeste homolog 2 (EZH2). Sanger sequencing of EZH2 in a third classically-affected proband identified a third de novo mutation in this gene. These data show that mutations in EZH2 cause Weaver syndrome. 相似文献
58.
Srour M Schwartzentruber J Hamdan FF Ospina LH Patry L Labuda D Massicotte C Dobrzeniecka S Capo-Chichi JM Papillon-Cavanagh S Samuels ME Boycott KM Shevell MI Laframboise R Désilets V;FORGE Canada Consortium Maranda B Rouleau GA Majewski J Michaud JL 《American journal of human genetics》2012,90(4):693-700
Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have not yet been identified in this family nor in most French Canadian individuals subsequently described. We ascertained a cluster of 16 JBTS-affected individuals from 11 families living in the Lower St. Lawrence region. SNP genotyping excluded the presence of a common homozygous mutation that would explain the clustering of these individuals. Exome sequencing performed on 15 subjects showed that nine affected individuals from seven families (including the original JBTS family) carried rare compound-heterozygous mutations in C5ORF42. Two missense variants (c.4006C>T [p.Arg1336Trp] and c.4690G>A [p.Ala1564Thr]) and a splicing mutation (c.7400+1G>A), which causes exon skipping, were found in multiple subjects that were not known to be related, whereas three other truncating mutations (c.6407del [p.Pro2136Hisfs*31], c.4804C>T [p.Arg1602*], and c.7477C>T [p.Arg2493*]) were identified in single individuals. None of the unaffected first-degree relatives were compound heterozygous for these mutations. Moreover, none of the six putative mutations were detected among 477 French Canadian controls. Our data suggest that mutations in C5ORF42 explain a large portion of French Canadian individuals with JBTS. 相似文献
59.
Franchini L Panza L Kongmanas K Tanphaichitr N Faull KF Ronchetti F 《Chemistry and physics of lipids》2008,152(2):78-85
Seminolipids 1a and 1b and galactosylalkylacylglycerols 2a and 2b, labelled with deuterium on the alkyl or acyl chain, respectively, were obtained isotopically and chemically pure through a straightforward synthesis from protected glycidyl galactoside 3 in an overall 22% yield. The identity and purity of compounds was ascertained by NMR spectroscopy and ESI mass spectrometry analysis. These labelled compounds are important as internal standards for quantification of these lipids by mass spectrometry, and they could also be used in metabolic studies in in vitro and even in vivo systems. Extension of the procedure could provide a route for the preparation of isotopomers of other compounds of the same general class. 相似文献
60.
Lanigan-Gerdes S Briceno G Dooley AN Faull KF Lazazzera BA 《Journal of bacteriology》2008,190(20):6668-6675
Extracellular Phr pentapeptides produced by gram-positive, spore-forming bacteria regulate processes during the transition from exponential- to stationary-phase growth. Phr pentapeptides are produced by cleavage of their precursor proteins. We determined the residues that direct this cleavage for the Bacillus subtilis Phr peptide, CSF, which is derived from the C terminus of PhrC. Strains expressing PhrC with substitutions in residues -1 to -5 relative to the cleavage site had a defect in CSF production. The mutant PhrC proteins retained a functional signal sequence for secretion, as assessed by secretion of PhrC-PhoA fusions. To determine whether the substitutions directly affected cleavage of PhrC to CSF, we tested cleavage of synthetic pro-CSF peptides that corresponded to the C terminus of PhrC and had an amino acid substitution at the -2, -3, or -4 position. The mutant pro-CSF peptides were cleaved less efficiently to CSF than the wild-type pro-CSF peptide whether they were incubated with whole cells, cell wall material, or the processing protease subtilisin or Vpr. To further define the range of amino acids that support CSF production, the amino acid at the -4 position of PhrC was replaced by the 19 canonical amino acids. Only four substitutions resulted in a >2-fold defect in CSF production, indicating that this position is relatively immune to mutational perturbations. These data revealed residues that direct cleavage of CSF and laid the groundwork for testing whether other Phr peptides are processed in a similar manner. 相似文献