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.

Intracellular signalling pathways regulating the adaptation of skeletal muscle to exercise and nutritional changes

The focus of the present review is to assimilate current knowledge concerning the differing signalling transduction cascades that control muscle mass development and affect skeletal muscle phenotype following exercise or nutritional uptake. Effects of mechanical loading on protein synthesis are discussed. Muscle growth control is regulated by the interplay of growth promoting and growth suppressing factors, which act in concert. Much emphasis has been placed on understanding how increases in the rate of protein synthesis are induced in skeletal muscle during the adaptive process. One key point to emerge is that protein synthesis following resistance exercise or increased nutrient availability is mediated through changes in signal transduction involving the phosphorylation of mTOR and sequential activation of downstream targets. On the other hand, AMPK activation plays an important role in the inhibition of protein synthesis by suppressing the function of multiple translation regulators of the mTOR signalling pathway in response to cellular energy depletion and low metabolic conditions. The effects of exercise and/or nutritional uptake on the activation of signalling molecules that regulate protein synthesis are highlighted, providing a better understanding of the molecular changes in the cell.

Adaptation and speciation: what can F-st tell us?

A useful way of summarizing genetic variability among different populations is through estimates of the inbreeding coefficient, F-st. Several recent studies have tried to use the distribution of estimates of F-st from individual genetic loci to detect the effects of natural selection. However, the promise of this approach has yet to be fully realized owing to the pervasive dogma that this distribution is highly dependent on demographic history. Here, I review recent theoretical results that indicate that the distribution of estimates of F-st is generally expected to be robust to the vagaries of demographic history. I suggest that analyses based on it provide a useful first step for identifying candidate genes that might be under selection, and explore the ways in which this information can be used in ecological and evolutionary studies.

Restrictions to the adaptation of influenza A virus H5 hemagglutinin to the human host

The binding specificities of a panel of avian influenza virus subtype H5 hemagglutinin (RA) proteins bearing mutations at key residues in the receptor binding site were investigated. The results demonstrate that two simultaneous mutations in the receptor binding site resulted in H5 RA binding in a pattern similar to that shown by human viruses. Coexpression of the ion channel protein, M2, from most avian and human strains tested protected H5 RA conformation during trafficking, indicating that no genetic barrier to the reassortment of the H5 surface antigen gene with internal genes of human viruses existed at this level.

Adaptation of an commercially available stabilised R/C helicopter to a fully autonomous surveillance UAV

This paper presents the development of an autonomous surveillance UAV that competed in the Ministry of Defence Grand Challenge 2008. In order to focus on higher-level mission control, the UAV is built upon an existing commercially available stabilised R/C helicopter platform. The hardware architecture is developed to allow for non-invasion integration with the existing stabilised platform, and to enable to the distributed processing of closed loop control and mission goals. The resulting control system proved highly successful and was capable of flying within 40knott gusts. The software and safety architectures were key to the success of the research and also hold the potential for use in the development of more complex system comprising of multiple UAVs.

Comparative genome analysis provides insights into the evolution and adaptation of Pseudomonas syringae pv. aesculi on Aesculus hippocastanum.

A recently emerging bleeding canker disease, caused by Pseudomonas syringae pathovar aesculi (Pae), is threatening European horse chestnut in northwest Europe. Very little is known about the origin and biology of this new disease. We used the nucleotide sequences of seven commonly used marker genes to investigate the phylogeny of three strains isolated recently from bleeding stem cankers on European horse chestnut in Britain (E-Pae). On the basis of these sequences alone, the E-Pae strains were identical to the Pae type-strain (I-Pae), isolated from leaf spots on Indian horse chestnut in India in 1969. The phylogenetic analyses also showed that Pae belongs to a distinct clade of P. syringae pathovars adapted to woody hosts. We generated genome-wide Illumina sequence data from the three E-Pae strains and one strain of I-Pae. Comparative genomic analyses revealed pathovar-specific genomic regions in Pae potentially implicated in virulence on a tree host, including genes for the catabolism of plant-derived aromatic compounds and enterobactin synthesis. Several gene clusters displayed intra-pathovar variation, including those encoding type IV secretion, a novel fatty acid biosynthesis pathway and a sucrose uptake pathway. Rates of single nucleotide polymorphisms in the four Pae genomes indicate that the three E-Pae strains diverged from each other much more recently than they diverged from I-Pae. The very low genetic diversity among the three geographically distinct E-Pae strains suggests that they originate from a single, recent introduction into Britain, thus highlighting the serious environmental risks posed by the spread of an exotic plant pathogenic bacterium to a new geographic location. The genomic regions in Pae that are absent from other P. syringae pathovars that infect herbaceous hosts may represent candidate genetic adaptations to infection of the woody parts of the tree.

Temperature and the development rates of thrips: evidence for a constraint on local adaptation?

Typically, the relationship between insect development and temperature is described by two characteristics: the minimum temperature needed for development to occur (T-min) and the number of day degrees required (DDR) for the completion of development. We investigated these characteristics in three English populations of Thrips major and T tabaci [Cawood, Yorkshire (N53degrees49', W1degrees7'); Boxworth, Cambridgeshire (N52degrees15', W0degrees1'); Silwood Park, Berkshire (N51degrees24', W0degrees38')], and two populations of Frankliniella occidentalis (Cawood; Silwood Park). While there were no significant differences among populations in either T-min (mean for T major = 7.0degreesC; T tabaci = 5.9degreesC; F. occidentalis = 6.7degreesC) or DDR (mean for T major = 229.9; T tabaci = 260.8; F occidentalis = 233.4), there were significant differences in the relationship between temperature and body size, suggesting the presence of geographic variation in this trait. Using published data, in addition to those newly collected, we found a negative relationship between T-min. and DDR for F occidentalis and T tabaci, supporting the hypothesis that a trade-off between T-min and DDR may constrain adaptation to local climatic conditions.

Scenarios as the basis for assessment of mitigation and adaptation

The possibilities and need for adaptation and mitigation depends on uncertain future developments with respect to socio-economic factors and the climate system. Scenarios are used to explore the impacts of different strategies under uncertainty. In this chapter, some scenarios are presented that are used in the ADAM project for this purpose. One scenario explores developments with no mitigation, and thus with high temperature increase and high reliance on adaptation (leading to 4oC increase by 2100 compared to pre-industrial levels). A second scenario explores an ambitious mitigation strategy (leading to 2oC increase by 2100 compared to pre-industrial levels). In the latter scenario, stringent mitigation strategies effectively reduces the risks of climate change, but based on uncertainties in the climate system a temperature increase of 3oC or more cannot be excluded. The analysis shows that, in many cases, adaptation and mitigation are not trade-offs but supplements. For example, the number of people exposed to increased water resource stress due to climate change can be substantially reduced in the mitigation scenario, but even then adaptation will be required for the remaining large numbers of people exposed to increased stress. Another example is sea level rise, for which adaptation is more cost-effective than mitigation, but mitigation can help reduce damages and the cost of adaptation. For agriculture, finally, only the scenario based on a combination of adaptation and mitigation is able to avoid serious climate change impacts.

Observed adaptation to climate change: UK evidence of transition to a well-adapting society

This paper investigates whether and to what extent a wide range of actors in the UK are adapting to climate change, and whether this is evidence of a social transition. We document evidence of over 300 examples of early adopters of adaptation practice to climate change in the UK. These examples span a range of activities from small adjustments (or coping) to building adaptive capacity, implementing actions and creating deeper systemic change in public and private organisations in a range of sectors. We find that adaptation in the UK has been dominated by government initiatives and has principally occurred in the form of research into climate change impacts. These actions within government stimulate a further set of actions at other scales in public agencies, regulatory agencies and regional government (or in the devolved administrations), though with little real evidence of climate change adaptation initiatives trickling down to local government level. The water supply and flood defence sectors, requiring significant investment in large scale infrastructure such as reservoirs and coastal defences, have invested more heavily in identifying potential impacts and adaptations. Economic sectors that are not dependent on large scale infrastructure appear to be investing far less effort and resources in preparing for climate change. We conclude that while the government-driven top-down targeted adaptation approach has generated anticipatory action at low cost, it may also have created enough niche activities to allow for diffusion of new adaptation practices in response to real or perceived climate change. These results have significant implications for how climate policy can be developed to support autonomous adaptors in the UK and other countries.

Self-organising neural networks for adaptive control

Self-organizing neural networks have been implemented in a wide range of application areas such as speech processing, image processing, optimization and robotics. Recent variations to the basic model proposed by the authors enable it to order state space using a subset of the input vector and to apply a local adaptation procedure that does not rely on a predefined test duration limit. Both these variations have been incorporated into a new feature map architecture that forms an integral part of an Hybrid Learning System (HLS) based on a genetic-based classifier system. Problems are represented within HLS as objects characterized by environmental features. Objects controlled by the system have preset targets set against a subset of their features. The system's objective is to achieve these targets by evolving a behavioural repertoire that efficiently explores and exploits the problem environment. Feature maps encode two types of knowledge within HLS — long-term memory traces of useful regularities within the environment and the classifier performance data calibrated against an object's feature states and targets. Self-organization of these networks constitutes non-genetic-based (experience-driven) learning within HLS. This paper presents a description of the HLS architecture and an analysis of the modified feature map implementing associative memory. Initial results are presented that demonstrate the behaviour of the system on a simple control task.

Using self-organising feature maps for the control of artificial organisms

Variations on the standard Kohonen feature map can enable an ordering of the map state space by using only a limited subset of the complete input vector. Also it is possible to employ merely a local adaptation procedure to order the map, rather than having to rely on global variables and objectives. Such variations have been included as part of a hybrid learning system (HLS) which has arisen out of a genetic-based classifier system. In the paper a description of the modified feature map is given, which constitutes the HLSs long term memory, and results in the control of a simple maze running task are presented, thereby demonstrating the value of goal related feedback within the overall network.

A review of climate risk information for adaptation and development planning

Although the use of climate scenarios for impact assessment has grown steadily since the 1990s, uptake of such information for adaptation is lagging by nearly a decade in terms of scientific output. Nonetheless, integration of climate risk information in development planning is now a priority for donor agencies because of the need to prepare for climate change impacts across different sectors and countries. This urgency stems from concerns that progress made against Millennium Development Goals (MDGs) could be threatened by anthropogenic climate change beyond 2015. Up to this time the human signal, though detectable and growing, will be a relatively small component of climate variability and change. This implies the need for a twin-track approach: on the one hand, vulnerability assessments of social and economic strategies for coping with present climate extremes and variability, and, on the other hand, development of climate forecast tools and scenarios to evaluate sector-specific, incremental changes in risk over the next few decades. This review starts by describing the climate outlook for the next couple of decades and the implications for adaptation assessments. We then review ways in which climate risk information is already being used in adaptation assessments and evaluate the strengths and weaknesses of three groups of techniques. Next we identify knowledge gaps and opportunities for improving the production and uptake of climate risk information for the 2020s. We assert that climate change scenarios can meet some, but not all, of the needs of adaptation planning. Even then, the choice of scenario technique must be matched to the intended application, taking into account local constraints of time, resources, human capacity and supporting infrastructure. We also show that much greater attention should be given to improving and critiquing models used for climate impact assessment, as standard practice. Finally, we highlight the over-arching need for the scientific community to provide more information and guidance on adapting to the risks of climate variability and change over nearer time horizons (i.e. the 2020s). Although the focus of the review is on information provision and uptake in developing regions, it is clear that many developed countries are facing the same challenges. Copyright © 2009 Royal Meteorological Society