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.

Local adaptation in moss life histories: population-level variation and a reciprocal transplant experiment

We examine the extent of population-level differentiation in life history traits of Pogonatum aloides, Polytrichum commune and Polytrichum juniperinum (Polytrichaceae) between upland and lowland localities within Britain. Reciprocal transplant studies are used to estimate the relative importance of genetic versus environmental effects on observed differences. We demonstrate significant life history differentiation between moss populations, and show that at least some of these are genetically determined, although environment and phenotypic plasticity are also significant components of the observed variation. The transplant experiments indicate divergence among populations in plasticity of male reproductive effort and of investment in vegetative shoots by females. Two tradeoffs are identified; one between the number and the size of spores, and the second between reproduction by spores versus vegetative reproduction. The patterns of life history variation observed between populations of Polytrichum juniperinum are consistent with selection along these implied tradeoff curves, and we propose that they reflect selective pressures arising from the spatial and demographic distribution of mortality at upland versus lowland sites. The results underscore the need for more studies of intra-specific life history variation in mosses.

Annexins: multifunctional components of growth and adaptation

Plant annexins are ubiquitous, soluble proteins capable of Ca2+-dependent and Ca2+-independent binding to endomembranes and the plasma membrane. Some members of this multigene family are capable of binding to F-actin, hydrolysing ATP and GTP, acting as peroxidases or cation channels. These multifunctional proteins are distributed throughout the plant and throughout the life cycle. Their expression and intracellular localization are under developmental and environmental control. The in vitro properties of annexins and their known, dynamic distribution patterns suggest that they could be central regulators or effectors of plant growth and stress signalling. Potentially, they could operate in signalling pathways involving cytosolic free calcium and reactive oxygen species.

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.

Preliterate phonological awareness and early literacy skills in Turkish

The role of preschool phonological awareness in early reading and spelling skills was investigated in the transparent orthography of Turkish. Fifty-six preschool children (mean age=5.6 years) were followed into Grade 2 (mean age=7.6 years). While preschool phonological awareness failed to make any reliable contribution to future reading skills, it was the strongest longitudinal correlate of spelling skills measured at the end of Grades 1 and 2. Overall findings suggested that phonological awareness may be differentially related to reading and spelling, and that spelling is a more sensitive index of phonological processing skills. In this study, verbal short-term memory emerged as the most powerful and consistent longitudinal correlate of reading speed. This finding raised important questions about the component processes of reading speed, and the role of memory and morphosyntactic skills in an agglutinative and transparent orthography such as Turkish.

The relationship between phonological awareness and word reading accuracy in Oriya and English: A Study of Oriya-speaking fifth-graders

This study investigated the relationships between phonological awareness and reading in Oriya and English. Oriya is the official language of Orissa, an eastern state of India. The writing system is an alphasyllabary. Ninety-nine fifth grade children (mean age 9 years 7 months) were assessed on measures of phonological awareness, word reading and pseudo-word reading in both languages. Forty-eight of the children attended Oriya-medium schools where they received literacy instruction in Oriya from grade 1 and learned English from grade 2. Fifty-one children attended English-medium schools where they received literacy instruction in English from grade 1 and in Oriya from grade 2. The results showed that phonological awareness in Oriya contributed significantly to reading Oriya and English words and pseudo-words for the children in the Oriya-medium schools. However, it only contributed to Oriya pseudo-word reading and English word reading for children in the English-medium schools. Phonological awareness in English contributed to English word and pseudo-word reading for both groups. Further analyses investigated the contribution of awareness of large phonological units (syllable, onsets and rimes) and small phonological units (phonemes) to reading in each language. The data suggest that cross-language transfer and facilitation of phonological awareness to word reading is not symmetrical across languages and may depend both on the characteristics of the different orthographies of the languages being learned and whether the first literacy language is also the first spoken language.

Phonological similarity effects without a phonological store: an individual differences model

The feature model of immediate memory (Nairne, 1990) is applied to an experiment testing individual differences in phonological confusions amongst a group (N=100) of participants performing a verbal memory test. By simulating the performance of an equivalent number of “pseudo-participants” the model fits both the mean performance and the variability within the group. Experimental data show that high-performing individuals are significantly more likely to demonstrate phonological confusions than low performance individuals and this is also true of the model, despite the model’s lack of either an explicit phonological store or a performance-linked strategy shift away from phonological storage. It is concluded that a dedicated phonological store is not necessary to explain the basic phonological confusion effect, and the reduction in such an effect can also be explained without requiring a change in encoding or rehearsal strategy or the deployment of a different storage buffer.

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.