Non-hemagglutinating flaviviruses: molecular mechanisms for the emergence of new strains via adaptation to European ticks

Tick-borne encephalitis virus (TBEV) causes human epidemics across Eurasia. Clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined. TBEV is characteristically a hemagglutinating (HA) virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity. However, for the past few years many atypical HA-deficient strains have been isolated from patients and also from the natural European host tick, Ixodes persulcatus. By analysing the sequences of HA-deficient strains we have identified 3 unique amino acid substitutions (D67G, E122G or D277A) in the envelope protein, each of which increases the net charge and hydrophobicity of the virion surface. Therefore, we genetically engineered virus mutants each containing one of these 3 substitutions; they all exhibited HA-deficiency. Unexpectedly, each genetically modified non-HA virus demonstrated increased TBEV reproduction in feeding Ixodes ricinus, not the recognised tick host for these strains. Moreover, virus transmission efficiency between infected and uninfected ticks co-feeding on mice was also intensified by each substitution. Retrospectively, the mutation D67G was identified in viruses isolated from patients with encephalitis. We propose that the emergence of atypical Siberian HA-deficient TBEV strains in Europe is linked to their molecular adaptation to local ticks. This process appears to be driven by the selection of single mutations that change the virion surface thus enhancing receptor/fusion function essential for TBEV entry into the unfamiliar tick species. As the consequence of this adaptive mutagenesis, some of these mutations also appear to enhance the ability of TBEV to cross the human blood-brain barrier, a likely explanation for fatal encephalitis. Future research will reveal if these emerging Siberian TBEV strains continue to disperse westwards across Europe by adaptation to the indigenous tick species and if they are associated with severe forms of TBE.

The impact of multiskilling on UK construction manpower

The overall significance of the construction and building services sector internationally cannot be overemphasised. In the UK, the industry currently accounts for 10% gross domestic product (GDP) and employs 2 million people, which is more than 1 in 14 of the total workforce. However, regardless of its output (approximately £65 billion annually) there has been a steady decline in the number of trade entrants into the construction and building services sector. Consequently, the available ‘pool of labour’ is inadequately resourced; productivity is low; the existing labour force is overstressed; there is an increase in site deaths; and a long-term labour shortage is envisaged. Today, the evidence seems to suggest that multiskilling is a tentative redress for ameliorating the skills crisis in the construction and building sectors. A 43-year time-series of data on 23 manpower attributes was evaluated as part of this investigation. The developed linear regression models show that the concept of multiskilling obeys the ‘law of diminishing returns'. That is, a weak relation was found between construction output and a three or more combination of manpower attributes. An optimisation model is prescribed for traditional trades.

Drivers of change in mountain farming in Slovakia: from socialist collectivisation to the Common Agricultural Policy

The transformations in Slovak agriculture from the 1950s to the present day, considering both the generic (National and EU) and site-specific (local) drivers of landscape change, were analysed in five mountain study areas in the country. An interdisciplinary approach included analysis of population trends, evaluation of land use and landscape change combined with exploration of the perceptions of local stakeholders and results of previous biodiversity studies. The generic processes active from the 1950s to 1970s were critical for all study areas with impacts lasting right up until the present day. Agricultural collectivisation, agricultural intensification and land abandonment had negative effects in all study areas. However, the precise impacts on the landscape were different in the different study areas due to site-specific attributes (e.g. population trends, geographic localisation and local attitudes and opportunities), and these played a decisive role in determining the trajectory of change. Regional contrasts in rural development between these territories have increased in the last two decades, also due to the imperfect preconditions of governmental support. The recent Common Agricultural Policy developments are focused on maintenance of intensive large-scale farming rather than direct enhancement of agro-biodiversity and rural development at the local scale. In this context, local, site-specific attributes can and must form an essential part of rural development plans, to meet the demands for management of the diversity of agricultural mountain landscapes and facilitate the multifunctional role of agriculture.