77 research outputs found

    The post-covid future of virtual conferences

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    For many researchers, 2020 will have been the first year in which they have attended any virtual academic events. In this cross-post Gina Sipley reflects on the advantages and disadvantages of virtual conferences and whether they may become a permanent fixture of the post-pandemic university

    The Revenge of Swamp Thing: Wetlands, Industrial Capitalism, and the Ecological Contradiction of Great Expectations

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    This essay places Charles Dickens' Great Expectations in the context of nineteenth-century understandings of England's wetlands. By offering a new reading of a well-known novel the essay seeks to understand the ecological inflection of Dickens' work, and more broadly the Victorian novel's mediation between environmental and socio-economic history. Focusing on the marshes as a space of criminality and liminality, composed partly of land and partly of water, partially industrialized and partially "wasted," this study argues that the construction of this space and its subjects as "criminal" derives from its very resistance to being made useful and (re)productive. More broadly, the essay suggests that a perspective combining ecocriticism with cultural materialism reveals how the novel's contradictory representations of nature are intimately related to the contradictory status of these peripheral spaces under the regime of industrial capitalism

    Escherichia coli YafP protein modulates DNA damaging property of the nitroaromatic compounds

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    Escherichia coli SOS functions constitute a multifaceted response to DNA damage. We undertook to study the role of yafP, a SOS gene with unknown function. yafP is part of an operon also containing the dinB gene coding for DNA Polymerase IV (PolIV). Our phylogenetic analysis showed that the gene content of this operon is variable but that the dinB and the yafP genes are conserved in the majority of E. coli natural isolates. Therefore, we studied if these proteins are functionally linked. Using a murine septicaemia model, we showed that YafP activity reduced the bacterial fitness in the absence of PolIV. Similarly, YafP increased cytotoxicity of two DNA damaging nitroaromatic compounds, 4-nitroquinoline-1-oxide (NQO) and nitrofurazone, in the absence of PolIV. The fact that PolIV counterbalances YafP-induced cytotoxicity could explain why these two genes are transcriptionally linked. We also studied the involvement of YafP in genotoxic-stress induced mutagenesis and found that PolIV and YafP reduced NQO-induced mutagenicity. The YafP antimutator activity was independent of the PolIV activity. Given that YafP was annotated as a putative acetyltransferase, it could be that YafP participates in the metabolic transformation of genotoxic compounds, hence modulating the balance between their mutagenicity and cytotoxicity

    FSscan: a mechanism-based program to identify +1 ribosomal frameshift hotspots

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    In +1 programmed ribosomal frameshifting (PRF), ribosomes skip one nucleotide toward the 3′-end during translation. Most of the genes known to demonstrate +1 PRF have been discovered by chance or by searching homologous genes. Here, a bioinformatic framework called FSscan is developed to perform a systematic search for potential +1 frameshift sites in the Escherichia coli genome. Based on a current state of the art understanding of the mechanism of +1 PRF, FSscan calculates scores for a 16-nt window along a gene sequence according to different effects of the stimulatory signals, and ribosome E-, P- and A-site interactions. FSscan successfully identified the +1 PRF site in prfB and predicted yehP, pepP, nuoE and cheA as +1 frameshift candidates in the E. coli genome. Empirical results demonstrated that potential +1 frameshift sequences identified promoted significant levels of +1 frameshifting in vivo. Mass spectrometry analysis confirmed the presence of the frameshifted proteins expressed from a yehP-egfp fusion construct. FSscan allows a genome-wide and systematic search for +1 frameshift sites in E. coli. The results have implications for bioinformatic identification of novel frameshift proteins, ribosomal frameshifting, coding sequence detection and the application of mass spectrometry on studying frameshift proteins

    Unique Cost Dynamics Elucidate the Role of Frameshifting Errors in Promoting Translational Robustness

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    There is now considerable evidence supporting the view that codon usage is frequently under selection for translational accuracy. There are, however, multiple forms of inaccuracy (missense, premature termination, and frameshifting errors) and pinpointing a particular error process behind apparently adaptive mRNA anatomy is rarely straightforward. Understanding differences in the fitness costs associated with different types of translational error can help us devise critical tests that can implicate one error process to the exclusion of others. To this end, we present a model that captures distinct features of frameshifting cost and apply this to 641 prokaryotic genomes. We demonstrate that, although it is commonly assumed that the ribosome encounters an off-frame stop codon soon after the frameshift and costs of mis-elongation are therefore limited, genomes with high GC content typically incur much larger per-error costs. We go on to derive the prediction, unique to frameshifting errors, that differences in translational robustness between the 5′ and 3′ ends of genes should be less pronounced in genomes with higher GC content. This prediction we show to be correct. Surprisingly, this does not mean that GC-rich organisms necessarily carry a greater fitness burden as a consequence of accidental frameshifting. Indeed, increased per-error costs are often more than counterbalanced by lower predicted error rates owing to more diverse anticodon repertoires in GC-rich genomes. We therefore propose that selection on tRNA repertoires may operate to reduce frameshifting errors

    Fluorescent T7 display phages obtained by translational frameshift

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    Lytic phages form a powerful platform for the display of large cDNA libraries and offer the possibility to screen for interactions with almost any substrate. To visualize these interactions directly by fluorescence microscopy, we constructed fluorescent T7 phages by exploiting the flexibility of phages to incorporate modified versions of its capsid protein. By applying translational frameshift sequences, helper plasmids were constructed that expressed a fixed ratio of both wild-type capsid protein (gp10) and capsid protein fused to enhanced yellow fluorescent protein (EYFP). The frameshift sequences were inserted between the 3′ end of the capsid gene and the sequence encoding EYFP. Fluorescent fusion proteins are only formed when the ribosome makes a −1 shift in reading frame during translation. Using standard fluorescence microscopy, we could sensitively monitor the enrichment of specific binders in a cDNA library displayed on fluorescent T7 phages. The perspectives of fluorescent display phages in the fast emerging field of single molecule detection and sorting technologies are discussed

    Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use.

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    Genetic decoding is not 'frozen' as was earlier thought, but dynamic. One facet of this is frameshifting that often results in synthesis of a C-terminal region encoded by a new frame. Ribosomal frameshifting is utilized for the synthesis of additional products, for regulatory purposes and for translational 'correction' of problem or 'savior' indels. Utilization for synthesis of additional products occurs prominently in the decoding of mobile chromosomal element and viral genomes. One class of regulatory frameshifting of stable chromosomal genes governs cellular polyamine levels from yeasts to humans. In many cases of productively utilized frameshifting, the proportion of ribosomes that frameshift at a shift-prone site is enhanced by specific nascent peptide or mRNA context features. Such mRNA signals, which can be 5' or 3' of the shift site or both, can act by pairing with ribosomal RNA or as stem loops or pseudoknots even with one component being 4 kb 3' from the shift site. Transcriptional realignment at slippage-prone sequences also generates productively utilized products encoded trans-frame with respect to the genomic sequence. This too can be enhanced by nucleic acid structure. Together with dynamic codon redefinition, frameshifting is one of the forms of recoding that enriches gene expression.This work was supported by grants from Science Foundation Ireland [12/IP/1492 and 13/1A/1853 to J.F.A; 12/IA/1335 to P.V.B.], US. National Institutes of Health [RO3 MH098688 to J.F.A.], the Wellcome Trust [106207 to A.E.F and 094423 to P.V.B.] and the European Research Council (ERC) grant No. 646891 to A.E.F.]This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/nar/gkw53

    Improving Vocal Self-Image and Tone Quality in Adolescent Girls: A Study

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    The Adolescent Female Voice: A Review of Related Literature

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    This paper discusses the research findings in voice mutation, vocal instruction, and the application of knowledge to vocal instruction. Much research involves changes in the male and female adolescent voices, especially of interest to choral directors and music educators. The research defines the vocal development categories as: (1) posture; (2) breath management; (3) relaxation; (4) phonation; (5) resonance; (6) registration; and (7) articulation. A segment on therapy and exercise suggests ways to develop the voice that has been abused. An extensive list of references offers further topics for research
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