L-selectin is essential for delivery of activated CD8+ T cells to virus-infected organs for protective immunity

Cytotoxic CD8+ T lymphocytes play a critical role in the host response to infection by viruses. The ability to secrete cytotoxic chemicals and cytokines is considered pivotal for eliminating virus. Of equal importance is how effector CD8+ T cells home to virus-infected tissues. L-selectin has not been considered important for effector T cell homing, because levels are low on activated T cells. We report here that, although L-selectin expression is downregulated following T cell priming in lymph nodes, L-selectin is re-expressed on activated CD8+ T cells entering the bloodstream, and recruitment of activated CD8+ T cells from the bloodstream into virus-infected tissues is L-selectin dependent. Furthermore, L-selectin on effector CD8+ T cells confers protective immunity to two evolutionally distinct viruses, vaccinia and influenza, which infect mucosal and visceral organs, respectively. These results connect homing and a function of virus-specific CD8+ T cells to a single molecule, L-selectin

Designing engaging online behaviour change interventions: a proposed model of user engagement

Camille E. Short, Amanda L. Rebar, Ronald C. Plotnikoff, Corneel Vandelanott

Validity and responsiveness to change of the Active Australia Survey according to gender, age, BMI, education, and physical activity level and awareness

© 2019 The Author(s). Background: This study aimed to investigate the validity of the Active Australia Survey across different subgroups and its responsiveness to change, as few previous studies have examined this. Methods: The Active Australia Survey was validated against the ActiGraph as an objective measure of physical activity. Participants (n = 465) wore the ActiGraph for 7 days and subsequently completed the Active Australia Survey. Moderate activity, vigorous activity and total moderate and vigorous physical activity were compared using Spearman rank-order correlations. Changes in physical activity between baseline and 3-month assessments were correlated to examine responsiveness to change. The data were stratified to assess outcomes according to different subgroups (e.g., gender, age, weight, activity levels). Results: With regards to the validity, a significant correlation of ρ = 0.19 was found for moderate physical activity, ρ = 0.33 for vigorous physical activity and ρ = 0.23 for moderate and vigorous physical activity combined. For vigorous physical activity correlations were higher than 0.3 for most subgroups, whereas they were only higher than 0.3 in those with a healthy weight for the other activity outcomes. With regards to responsiveness to change, a correlation of ρ = 0.32 was found for moderate physical activity, ρ = 0.19 for vigorous physical activity and ρ = 0.35 for moderate and vigorous physical activity combined. For moderate and vigorous activity combined correlations were higher than 0.4 for several subgroups, but never for vigorous physical activity. Conclusions: Little evidence for the validity of Active Australia Survey was found, although the responsiveness to change was acceptable for several subgroups. Findings from studies using the Active Australia Survey should be interpreted with caution. Trial registration: World Health Organisation Universal Trial Number: U111-1119-1755. Australian New Zealand Clinical Trials Registry, ACTRN12611000157976. Registration date: 8 March 2011

Adaptive evolution of synchronous egg-hatching in compensation for the loss of parental care.

Interactions among siblings are finely balanced between rivalry and cooperation, but the factors that tip the balance towards cooperation are incompletely understood. Previous observations of insect species suggest that (i) sibling cooperation is more likely when siblings hatch at the same time, and (ii) this is more common when parents provide little to no care. In this paper, we tested these ideas experimentally with the burying beetle, Nicrophorus vespilloides Burying beetles convert the body of a small dead vertebrate into an edible nest for their larvae, and provision and guard their young after hatching. In our first experiment, we simulated synchronous or asynchronous hatching by adding larvae at different intervals to the carrion-breeding resource. We found that 'synchronously' hatched broods survived better than 'asynchronously' hatched broods, probably because 'synchronous hatching' generated larger teams of larvae, that together worked more effectively to penetrate the carrion nest and feed upon it. In our second experiment, we measured the synchronicity of hatching in experimental populations that had evolved for 22 generations without any post-hatching care, and control populations that had evolved in parallel with post-hatching care. We found that larvae were more likely to hatch earlier, and at the same time as their broodmates, in the experimental populations that evolved without post-hatching care. We suggest that synchronous hatching enables offspring to help each other when parents are not present to provide care. However, we also suggest that greater levels of cooperation among siblings cannot compensate fully for the loss of parental care

Automatic evaluation stimuli - the most frequently used words to describe physical activity and the pleasantness of physical activity

Physical activity is partially regulated by non-conscious processes including automatic evaluations - the spontaneous affective reactions we have to physical activity that lead us to approach or avoid physical activity opportunities. A sound understanding of which words best represent the concepts of physical activity and pleasantness (as associated with physical activity) is needed to improve the measurement of automatic evaluations and related constructs (e.g., automatic self-schemas, attentional biases). The first aim of this study was to establish population-level evidence of the most common word stimuli for physical activity and pleasantness. Given that response latency measures have been applied to assess automatic evaluations of physical activity and exercise, the second aim was to determine whether people use the same behavior and pleasant descriptors for physical activity and exercise. Australian adults (N = 1,318; 54.3% women; 48.9% aged 55 years or older) were randomly assigned to one of two groups, through a computer-generated 1:1 ratio allocation, to be asked to list either five behaviors and pleasant descriptors of physical activity (n = 686) or of exercise (n = 632). The words were independently coded twice as to whether they were novel words or the same as another (i.e., same stem or same meaning). Intercoder reliability varied between moderate and strong (agreement = 50.1 to 97.8%; κ = 0.48 to 0.82). A list of the 20 most common behavior and pleasantness words were established based on how many people reported them, weighted by the ranking (1-5) people gave them. The words people described as physical activity were mostly the same as those people used to describe exercise. The most common behavior words were 'walking,' 'running,' 'swimming,' 'bike riding,' and 'gardening'; and the most common pleasant descriptor words were 'relaxing,' 'happiness,' 'enjoyment,' 'exhilarating,' 'exhausting,' and 'good.' These sets of stimuli can be utilized as resources for response latency measurement tasks of automatic evaluations and for tools to enhance automatic evaluations of physical activity in evaluative conditioning tasks.Amanda L. Rebar, Stephanie Schoeppe, Stephanie J. Alley, Camille E. Short, James A. Dimmock, Ben Jackson, David E. Conroy, Ryan E. Rhodes and Corneel Vandelanott

Physical activity screening to recruit inactive randomized controlled trial participants: how much is too much?

Citation: Vandelanotte, C., Stanton, R., Rebar, A. L., Van Itallie, A. K., Caperchione, C. M., Duncan, M. J., . . . Kolt, G. S. (2015). Physical activity screening to recruit inactive randomized controlled trial participants: how much is too much? Trials, 16, 3. doi:10.1186/s13063-015-0976-7Screening physical activity levels is common in trials to increase physical activity in inactive populations. Commonly applied single-item screening tools might not always be effective in identifying those who are inactive. We applied the more extensive Active Australia Survey to identify inactive people among those who had initially been misclassified as too active using a single-item measure. Those enrolled after the Active Australia Survey screening had significantly higher physical activity levels at subsequent baseline assessment. Thus, more extensive screening measures might result in the inclusion of participants who would otherwise be excluded, possibly introducing unwanted bias

Purity of transferred CD8+ T cells is crucial for safety and efficacy of combinatorial tumor immunotherapy in the absence of SHP-1

Adoptive transfer of tumor-specific cytotoxic T cells is a promising advance in cancer therapy. Similarly, checkpoint inhibition has shown striking clinical results in some patients. Here we combine adoptive cell transfer with ablation of the checkpoint protein Src homology 2-domain-containing phosphatase 1 (SHP-1, Ptpn6). Naturally occurring motheaten mice lack SHP-1 and do not survive weaning due to extensive immunopathology. To circumvent this limitation, we created a novel SHP-1(null) mouse that is viable up to 12 weeks of age by knocking out IL1r1. Using this model, we demonstrate that the absence of SHP-1 augments the ability of adoptively transferred CD8(+) T cells to control tumor growth. This therapeutic effect was only observed in situations where T-cell numbers were limited, analogous to clinical settings. However, adoptive transfer of non-CD8(+) SHP-1(null) hematopoietic cells resulted in lethal motheaten-like pathology, indicating that systemic inhibition of SHP-1 could have serious adverse effects. Despite this caveat, our findings support the development of SHP-1 inhibition strategies in human T cells to complement adoptive transfer therapies in the clinic

Sexual selection and population divergence I. the influence of socially flexible cuticular hydrocarbon expression in male field crickets (Teleogryllus oceanicus).

This is the peer reviewed version of the article which has been published in final form at DOI: 10.1111/evo.12839.© 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.Debates about how coevolution of sexual traits and preferences might promote evolutionary diversification have permeated speciation research for over a century. Recent work demonstrates that the expression of such traits can be sensitive to variation in the social environment. Here we examined social flexibility in a sexually selected male trait - cuticular hydrocarbon (CHC) profiles - in the field cricket Teleogryllus oceanicus and tested whether population genetic divergence predicts the extent or direction of social flexibility in allopatric populations. We manipulated male crickets' social environments during rearing and then characterised CHC profiles. CHC signatures varied considerably across populations and also in response to the social environment, but our prediction that increased social flexibility would be selected in more recently founded populations exposed to fluctuating demographic environments was unsupported. Furthermore, models examining the influence of drift and selection failed to support a role of sexual selection in driving population divergence in CHC profiles. Variation in social environments might alter the dynamics of sexual selection, but our results align with theoretical predictions that the role social flexibility plays in modulating evolutionary divergence depends critically on whether responses to variation in the social environment are homogeneous across populations, or whether gene-by-social-environment interactions occur. This article is protected by copyright. All rights reserved.Natural Environment Research Council (NERC)University of California Pacific Rim Research GrantRoyal SocietyBiotechnology and Biological Sciences Research Council (BBSRC)Erasmus Exchang

Sexual selection and population divergence I. The influence of socially flexible cuticular hydrocarbon expression in male field crickets (Teleogryllus oceanicus)

Debates about how coevolution of sexual traits and preferences might promote evolutionary diversification have permeated speciation research for over a century. Recent work demonstrates that the expression of such traits can be sensitive to variation in the social environment. Here we examined social flexibility in a sexually selected male trait – cuticular hydrocarbon (CHC) profiles – in the field cricket Teleogryllus oceanicus and tested whether population genetic divergence predicts the extent or direction of social flexibility in allopatric populations. We manipulated male crickets’ social environments during rearing and then characterised CHC profiles. CHC signatures varied considerably across populations and also in response to the social environment, but our prediction that increased social flexibility would be selected in more recently founded populations exposed to fluctuating demographic environments was unsupported. Furthermore, models examining the influence of drift and selection failed to support a role of sexual selection in driving population divergence in CHC profiles. Variation in social environments might alter the dynamics of sexual selection, but our results align with theoretical predictions that the role social flexibility plays in modulating evolutionary divergence depends critically on whether responses to variation in the social environment are homogeneous across populations, or whether gene-by-social-environment interactions occur.PostprintPeer reviewe

Associations between quality of life and duration and frequency of physical activity and sedentary behaviour: Baseline findings from the WALK 2.0 randomised controlled trial.

While physical and mental health benefits of regular physical activity are well known, increasing evidence suggests that limiting sedentary behaviour is also important for health. Evidence shows associations of physical activity and sedentary behaviour with health-related quality of life (HRQoL), however, these findings are based predominantly on duration measures of physical activity and sedentary behaviour (e.g., minutes/week), with less attention on frequency measures (e.g., number of bouts). We examined the association of HRQoL with physical activity and sedentary behaviour, using both continuous duration (average daily minutes) and frequency (average daily bouts≥10 min) measures. Baseline data from the WALK 2.0 trial were analysed. WALK 2.0 is a randomised controlled trial investigating the effects of Web 2.0 applications on engagement, retention, and subsequent physical activity change. Daily physical activity and sedentary behaviour (duration = average minutes, frequency = average number of bouts ≥10 minutes) were measured (ActiGraph GT3X) across one week, and HRQoL was assessed with the 'general health' subscale of the RAND 36-Item Health Survey. Structural equation modelling was used to evaluate associations. Participants (N = 504) were 50.8±13.1 (mean±SD) years old with a BMI of 29.3±6.0. The 465 participants with valid accelerometer data engaged in an average of 24.0±18.3 minutes and 0.64±0.74 bouts of moderate-vigorous physical activity per day, 535.2±83.8 minutes and 17.0±3.4 bouts of sedentary behaviour per day, and reported moderate-high general HRQoL (64.5±20.0). After adjusting for covariates, the duration measures of physical activity (path correlation = 0.294, p<0.05) and sedentary behaviour were related to general HRQoL (path coefficient = -0.217, p<0.05). The frequency measure of physical activity was also significant (path coefficient = -0.226, p<0.05) but the frequency of sedentary behaviour was not significantly associated with general HRQoL. Higher duration levels of physical activity in fewer bouts, and lower duration of sedentary behaviour are associated with better general HRQoL. Further prospective studies are required to investigate these associations in different population groups over time