Translational control of SEPT9 isoforms is perturbed in disease

A common feature of the mammalian septin gene family is complex genomic architecture with multiple alternate splice variants. Septin 9 has 18 distinct transcripts encoding 15 polypeptides, with two transcripts (SEPT9_v4 and v4*) encoding the same polypeptide. We have previously reported that the ratio of these distinct transcripts is altered in neoplasia, with the v4 transcript being the usual form in normal cells but v4* becoming predominant in tumours. This led us to ask what the functional differences between these two transcripts might be. The 5'-UTRs of v4 and v4* have distinct 5' ends encoded by exons 1 beta (v4) and 1 zeta and 2 (v4*) and a common 3' region and initiating ATG encoded within exon 3. Here we show that the two mRNAs are translated with different efficiencies and that cellular stress can alter this. A putative internal ribosome entry site can be identified in the common region of the v4 and v4* 5'-UTRs and translation is modulated by an upstream open-reading frame in the unique region of the v4 5'-UTR. Germline mutations in hereditary neuralgic amyotrophy (HNA) map to the region which is common to the two UTRs. These mutations dramatically enhance the translational efficiency of the v4 5'-UTR, leading to elevated SEPT9_v4 protein under hypoxic conditions. Our data provide a mechanistic insight into how the HNA mutations can alter the fine control of SEPT9_v4 protein and its regulation under physiologically relevant conditions and are consistent with the episodic and stress-induced nature of the clinical features of HNA.

Extending Zipf’s law to n-grams for large corpora

Experiments show that for a large corpus, Zipf’s law does not hold for all rank of words: the frequencies fall below those predicted by Zipf’s law for ranks greater than about 5,000 word types in the English language and about 30,000 word types in the inflected languages Irish and Latin. It also does not hold for syllables or words in the syllable-based languages, Chinese or Vietnamese. However, when single words are combined together with word n-grams in one list and put in rank order, the frequency of tokens in the combined list extends Zipf’s law with a slope close to -1 on a log-log plot in all five languages. Further experiments have demonstrated the validity of this extension of Zipf’s law to n-grams of letters, phonemes or binary bits in English. It is shown theoretically that probability theory
alone can predict this behavior in randomly created n-grams of binary bits.

Stylistics, criticism and mythrepresentation again: squaring the circle with Ray Mackay's subjective solution for all problems

This article is a response to an article by Ray Mackay (1996) which constitutes an attack on stylistic analysis in general, and the writings of the above authors and Ron Carter in particular. Mackay's article (in Language and Communication) accuses stylistics of 'scientificness' and claims that its attempt to provide objective analyses of literary texts is futile.1 We suggest that Mackay has misrepresented what stylisticians have said about objectivity, and that his understanding of objectivity, science and the nature of text-interpretative argument is seriously flawed.

Teaching stylistics: analysing cohesion and narrative structure in a short story by Ernest Hemingway

The main aim of this article is to propose an exercise in stylistic analysis which can be employed in the teaching of English language. It details the design and results of a workshop activity on narrative carried out with undergraduates in a university department of English. The methods proposed are intended to enable students to obtain insights into aspects of cohesion and narrative structure; insights, it is suggested, which are not as readily obtainable through more traditional techniques of stylistic analysis. The text chosen for analysis is a short story by Ernest Hemingway comprising only 11 sentences. A jumbled version of this story is presented to students who are asked to assemble a cohesive and well-formed version of the story. Their (re)constructions are then compared with the original Hemingway version. Much interest, it is argued, lies in the ways in which the students justify their own versions in terms of their expectations about well-formedness in narrative. The activity is also intended to encourage students to see literary texts as a valuable means of providing insights into the subtleties of linguistic form and function.