Manipulation of flavour and aroma compound sequestration and release using a glycosyltransferase with specificity for terpene alcohols.

Glycosides are an important potential source of aroma and flavour compounds for release as volatiles in flowers and fruit. The production of glycosides is catalysed by UDP-glycosyltransferases (UGTs) that mediate the transfer of an activated nucleotide sugar to acceptor aglycones. A screen of UGTs expressed in kiwifruit (Actinidia deliciosa) identified the gene AdGT4 which was highly expressed in floral tissues and whose expression increased during fruit ripening. Recombinant AdGT4 enzyme glycosylated a range of terpenes and primary alcohols found as glycosides in ripe kiwifruit. Two of the enzyme's preferred alcohol aglycones, hexanol and (Z)-hex-3-enol, contribute strongly to the 'grassy-green' aroma notes of ripe kiwifruit and other fruit including tomato and olive. Transient over-expression of AdGT4 in tobacco leaves showed that enzyme was able to glycosylate geraniol and octan-3-ol in planta whilst transient expression of an RNAi construct in Actinidia eriantha fruit reduced accumulation of a range of terpene glycosides. Stable over-expression of AdGT4 in transgenic petunia resulted in increased sequestration of hexanol and other alcohols in the flowers. Transgenic tomato fruit stably over-expressing AdGT4 showed changes in both the sequestration and release of a range of alcohols including 3-methylbutanol, hexanol and geraniol. Sequestration occurred at all stages of fruit ripening. Ripe fruit sequestering high levels of glycosides were identified as having a less intense, earthier aroma in a sensory trial. These results demonstrate the importance of UGTs in sequestering key volatile compounds in planta and suggest a future approach to enhancing aromas and flavours in flowers and during fruit ripening. Yauk YK1, Ged C, Wang MY, Matich AJ, Tessarotto L, Cooney JM, Chervin C, Atkinson RG

Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes

Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Canny good, or quite canny? The semantic-syntactic distribution of canny in the North East of England

The word canny has long been associated with the dialects of the North East of England, most typically in its adjectival sense. However, it has four distinct functions (adjective, adverb, intensifier and modifier in quantifying expressions), which this paper tracks in a diachronic speech corpus. Although the intensifier (e.g. it’s canny good) is documented in the Survey of English Dialects (Upton, Parry and Widowson 1994), it appears in the corpus later than expected with the profile of an incoming form. Results from a judgement task corroborate the corpus trends and show that people’s intuitions about intensifier canny correlate with age as well as the semantics and position of the following adjective, in such a way that shows the intensifier is not fully delexicalised. The present research highlights the value of combining production and perception data in establishing how the origins of a linguistic item affect its distribution in its new function

Can big data solve a big problem? Reporting the obesity data landscape in line with the Foresight obesity system map.

BACKGROUND: Obesity research at a population level is multifaceted and complex. This has been characterised in the UK by the Foresight obesity systems map, identifying over 100 variables, across seven domain areas which are thought to influence energy balance, and subsequent obesity. Availability of data to consider the whole obesity system is traditionally lacking. However, in an era of big data, new possibilities are emerging. Understanding what data are available can be the first challenge, followed by an inconsistency in data reporting to enable adequate use in the obesity context. In this study we map data sources against the Foresight obesity system map domains and nodes and develop a framework to report big data for obesity research. Opportunities and challenges associated with this new data approach to whole systems obesity research are discussed. METHODS: Expert opinion from the ESRC Strategic Network for Obesity was harnessed in order to develop a data source reporting framework for obesity research. The framework was then tested on a range of data sources. In order to assess availability of data sources relevant to obesity research, a data mapping exercise against the Foresight obesity systems map domains and nodes was carried out. RESULTS: A reporting framework was developed to recommend the reporting of key information in line with these headings: Background; Elements; Exemplars; Content; Ownership; Aggregation; Sharing; Temporality (BEE-COAST). The new BEE-COAST framework was successfully applied to eight exemplar data sources from the UK. 80% coverage of the Foresight obesity systems map is possible using a wide range of big data sources. The remaining 20% were primarily biological measurements often captured by more traditional laboratory based research. CONCLUSIONS: Big data offer great potential across many domains of obesity research and need to be leveraged in conjunction with traditional data for societal benefit and health promotion

Sepsis-related deaths in the at-risk population on the wards: attributable fraction of mortality in a large point-prevalence study

Objective Sepsis mortality is reported to be high worldwide, however recently the attributable fraction of mortality due to sepsis (AFsepsis) has been questioned. If improvements in treatment options are to be evaluated, it is important to know what proportion of deaths are potentially preventable or modifiable after a sepsis episode. The aim of the study was to establish the fraction of deaths directly related to the sepsis episode on the general wards and emergency departments. Results 839 patients were recruited over the two 24-h periods in 2016 and 2017. 521 patients fulfilled SEPSIS-3 criteria. 166 patients (32.4%) with sepsis and 56 patients (17.6%) without sepsis died within 90 days. Out of the 166 sepsis deaths 12 (7.2%) could have been directly related to sepsis, 28 (16.9%) possibly related and 96 (57.8%) were not related to sepsis. Overall AFsepsis was 24.1%. Upon analysis of the 40 deaths likely to be attributable to sepsis, we found that 31 patients (77.5%) had the Clinical Frailty Score ≥ 6, 28 (70%) had existing DNA-CPR order and 17 had limitations of care orders (42.5%)