Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

<b>BACKGROUND:</b> The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.<p></p> <b>RESULTS:</b> Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.<p></p> <b>CONCLUSIONS:</b> Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

The Embodiment of Success and Failure as Forward versus Backward Movements

People often speak of success (e.g., “advance”) and failure (e.g., “setback”) as if they were forward versus backward movements through space. Two experiments sought to examine whether grounded associations of this type influence motor behavior. In Experiment 1, participants categorized success versus failure words by moving a joystick forward or backward. Failure categorizations were faster when moving backward, whereas success categorizations were faster when moving forward. Experiment 2 removed the requirement to categorize stimuli and used a word rehearsal task instead. Even without Experiment 1’s response procedures, a similar cross-over interaction was obtained (e.g., failure memorizations sped backward movements relative to forward ones). The findings are novel yet consistent with theories of embodied cognition and self-regulation

Communicating Information on Eruptions and Their Impacts from the Earliest Times Until the Late Twentieth Century

Volcanoes hold a fascination for human beings and, before they were recorded by literate observers, eruptions were portrayed in art, were recalled in legends and became incorporated into religious practices: being viewed as agents of punishment, bounty or intimidation depending upon their state of activity and the culture involved. In the Middle East the earliest depiction of an eruption is a wall painting dating from the Neolithic at Çatal Hüyük and the earliest record dates from the third millennium BCE. Knowledge of volcanoes increased over time. In some parts of the world knowledge of eruptions was passed down by oral transmission, but as far as written records were concerned, in the first century CE only 9 volcanoes in the Mediterranean region were recognised, together with Mount Cameroon in West Africa. In the next 1000 years the list grew by 17, some 14 of these volcanoes being in Japan. The first recorded eruptions in Indonesia occurred in 1000 and 1006, and volcanoes in newly settled Iceland increased the number to just 48 in 1380 CE. After this the list continued to increase, with important regions such as New Zealand and Hawaii only being added in the past 200 years. Only from 1900 did the rate of growth decline significantly (Simkin et al. 1981: 23; Simkin, 1993 Siebert et al. 2011; Simkin, 1993), but it is sobering to recall that in the twentieth century major eruptions have occurred from volcanoes that were considered inactive or extinct examples including: Mount Lamington - Papua New Guinea, 1951; Mount Arenal - Costa Rica, 1968 and Nyos - Cameroon, 1986. Although there are instances where the human impact of historical eruptions have been compiled - with examples including the 1883 eruption of Krakatau (Simkin and Fiske (1983) and 1943 -1952 eruption of Parícutin (Luhr and Simkin, 1993) - these are exceptions and there remains a significant gap in knowledge about both the short and long-term effects on societies of major eruptions which occurred before the 1980s. Following a broad review the chapter provides a discussion of the ways in which information has been collected, compiled and disseminated from the earliest times until the 1980s in two case study areas: the Azores Islands (Portugal) and southern Italy. In Italy information on eruptions stretches back to prehistoric times and has become progressively better known over more than 2,000 years of written history, yet even here there remain significant gaps in the record even for events that took place between 1900 and 1990. In contrast, located in the middle of the Atlantic, the Azores have been isolated for much of their history and illustrate the difficulties involved in using indigenous sources to compile, not only assessments of impact, but also at a more basic level a complete list of historical events with accurate dates