Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants.

Lorrie Moore collection, 'A Little Ethnic Kink Is Always Good to See”: Jewish performance anxiety and anti-passing in the fiction of Lorrie Moore

This essay explores the ways in which the performance of Jewish identity (in the sense both of representing Jewish characters and of writing about those characters’ conscious and unconscious renditions of their Jewishness) is a particular concern (in both senses of the word) for Lorrie Moore. Tracing Moore's representations of Jewishness over the course of her career, from the early story “The Jewish Hunter” through to her most recent novel, A Gate at the Stairs, I argue that it is characterized by (borrowing a phrase from Moore herself) “performance anxiety,” an anxiety that manifests itself in awkward comedy and that can be read both in biographical terms and as an oblique commentary on, or reworking of, the passing narrative, which I call “anti-passing.” Just as passing narratives complicate conventional ethno-racial definitions so Moore's anti-passing narratives, by representing Jews who represent themselves as other to themselves, as well as to WASP America, destabilize the category of Jewishness and, by implication, deconstruct the very notion of ethnic categorization.

Translating Lucretia: word, image and 'ethical non-indifference' in Simon de Hesdin's translation of Valerius Maximus's 'Facta et dicta memorabilia'

An analysis of how illustrations functioned as a distinctive and important aspect of the translation of Latin versions of the story of the rape and suicide of Lucretia into Middle French texts, especially the 'Faits et dits memorables' (a translation-adaptation of Valerius Maximus's 'Facta et dicta memorabilia'). The study focuses on a selection of 14th- and 15th- century illuminations, and proposes also that the early modern 'Lucretia' portrait tradition should be viewed in the context of these images.

Conjecture, proof, and sense in Wittgenstein's philosophy of mathematics

One of the key tenets in Wittgenstein’s philosophy of mathematics is that a mathematical proposition gets its meaning from its proof. This seems to have the paradoxical consequence that a mathematical conjecture has no meaning, or at least not the same meaning that it will have once a proof has been found. Hence, it would appear that a conjecture can never be proven true: for what is proven true must ipso facto be a different proposition from what was only conjectured. Moreover, it would appear impossible that the same mathematical proposition be proven in different ways. — I will consider some of Wittgenstein’s remarks on these issues, and attempt to reconstruct his position in a way that makes it appear less paradoxical.

Spoken word recognition in adolescents with autism spectrum disorders and specific language impairment

Spoken word recognition, during gating, appears intact in specific language impairment (SLI). This study used gating to investigate the process in adolescents with autism spectrum disorders plus language impairment (ALI). Adolescents with ALI, SLI, and typical language development (TLD), matched on nonverbal IQ listened to gated words that varied in frequency (low/high) and number of phonological onset neighbors (low/high density). Adolescents with ALI required more speech input to initially identify low-frequency words with low competitor density than those with SLI and those with TLD, who did not differ. These differences may be due to less well specified word form representations in ALI.

Investigating orthographic and semantic aspects of word learning in poor comprehenders

This study compared orthographic and semantic aspects of word learning in children who differed in reading comprehension skill. Poor comprehenders and controls matched for age (9-10 years), nonverbal ability and decoding skill were trained to pronounce 20 visually presented nonwords, 10 in a consistent way and 10 in an inconsistent way. They then had an opportunity to infer the meanings of the new words from story context. Orthographic learning was measured in three ways: the number of trials taken to learn to pronounce nonwords correctly, orthographic choice and spelling. Across all measures, consistent items were easier than inconsistent items and poor comprehenders did not differ from control children. Semantic learning was assessed on three occasions, using a nonword-picture matching task. While poor comprehenders showed equivalent semantic learning to controls immediately after exposure to nonword meaning, this knowledge was not well retained over time. Results are discussed in terms of the language and reading skills of poor comprehenders and in relation to current models of reading development.

Putting the S-word back into Sustainability: Can we be more social?

In an era dominated by climate change debate and environmentalism there is a real danger that the important ‘social’ pillar of sustainability drops out of our vocabulary. This can happen at a variety of scales from business level through to building and neighbourhood level regeneration and development. Social sustainability should be at the heart of all housing and mixed-use development but for a variety of reasons tends to be frequently underplayed. The recent English city riots have brought this point back sharply into focus. The relationships between people, places and the local economy all matter and this is as true today as it was in the late 19th century when Patrick Geddes, the great pioneering town planner and ecologist, wrote of ‘place-work-folk’. This paper, commissioned from Tim Dixon, explains what is meant by social sustainability (and how it is linked to concepts such as social capital and social cohesion); why the debate matters during a period when ‘localism’ is dominating political debate; and what is inhibiting its growth and its measurement. The paper reviews best practice in post-occupancy social sustainability metric systems, based on recent research undertaken by the author on Dockside Green in Vancouver, and identifi es some of the key operational issues in mainstreaming the concept within major mixed-use projects. The paper concludes by offering a framework for the key challenges faced in setting strategic corporate goals and objectives; prioritising and selecting the most appropriate investments; and measuring social sustainability performance by identifying the required data sources

Lorrie Moore: Mo(o)re than an interim assessment

Lorrie Moore has long shed the image of the precocious talent who won the Seventeen story prize with her first submission as a nineteen-year-old undergraduate, but there is still a sense that her best work may be yet to come. In that respect, this mini special issue represents by no means the final word on Moore, but rather an interim assessment of a career that is already substantial and that promises much more to come. Together these three essays (and introduction) offer a coherent and striking exploration of Moore's work that develops new directions for future criticism and will help cement her growing reputation as one of the most original and distinctive contemporary writers. They sometimes circle around the same stories, even the same quotations, reading them in a variety of frames and picking up (and at) the nuances of Moore's sustained wordplay and careful documenting of space, of identity, of gender. Thus these essays work together rather than separately, layering over multiple understandings of Moore's incisive American literature.