Hyperphenylalaninemia with high levels of 7-biopterin is associated with mutations in the PCBD gene encoding the bifunctional protein pterin-4a-carbinolamine dehydratase and transcriptional coactivator (DCoH).

Pterin-4a-carbinolamine dehydratase (PCD) is required for efficient tetrahydrobiopterin regeneration after phenylalanine hydroxylase activity. This catalytic function was proposed to be specifically defective in newborns with a mild form of hyperphenylalaninemia (HPA) and persistent high urinary levels of primapterin (7-biopterin). A second regulatory task of the same protein is DCoH, a coactivation of transcription by hepatocyte nuclear factor 1alpha (HNF-1alpha), a function that is apparently not impaired in these HPA individuals. It has been shown elsewhere that the human PCD/DCoH bifunctional protein is encoded by a single 4-exon-containing gene, PCBD, located on chromosome 10q22. We have now examined the PCBD gene for mutations at the genomic level in six such HPA patients from four different families. By the use of new intron-specific primers, we detected, in all six patients, single, homozygous nucleotide alterations, in exon 4, that were inherited from their parents. These homozygous alterations predicted mutant PCD/DCoH with a single amino acid exchange, in two cases (alleles T78I), or premature stop codons, in the other four patients (alleles E86X and Q97X). Recombinant expression in Escherichia coli revealed that the mutant proteins-T78I, E86X, and Q97X-are almost entirely in the insoluble fraction, in contrast to wild type, which is expressed as a soluble protein. These data support the proposal that HPA in combination with urinary primapterin may be due to autosomal recessive inheritance of mutations in the PCBD gene specifically affecting the dehydratase activity

The Queen’s speech : desecuritizing the past, present and future of Anglo-Irish relations

This article adopts the Copenhagen School’s concept of desecuritization to analyse the gestures of reconciliation undertaken during the 2011 state visit of Queen Elizabeth II to the Republic of Ireland, including her willingness to speak in Gaeilge at Dublin Castle. In the process, it opens new pathways to explore if, when and how desecuritizing moves can become possible. To respond to these questions, this article advances the concept of bilingual speech acts as a nuanced yet fruitful way to tease out the complexities of security speech and (de)securitization processes. It is also suggested that the concept of bilingual speech acts provides a way to respond to calls to include translation in critical security and securitization studies. However, while acknowledging the importance of these calls, it is shown that paying attention to bilingual speech acts demonstrates what can also be lost in translation. Empirically this article provides an in-depth analysis of the 2011 state visit to unpack the different kinds of desecuritizing moves that were undertaken in this context as well as the different modalities of security speech that were in play. To conclude, the merit of bilingual speech acts for understanding how to speak security in different ways and vocabularies are discussed.PostprintPeer reviewe