Predator Dispersal Determines the Effect of Connectivity on Prey Diversity

Linking local communities to a metacommunity can positively affect diversity by enabling immigration of dispersal-limited species and maintenance of sink populations. However, connectivity can also negatively affect diversity by allowing the spread of strong competitors or predators. In a microcosm experiment with five ciliate species as prey and a copepod as an efficient generalist predator, we analysed the effect of connectivity on prey species richness in metacommunities that were either unconnected, connected for the prey, or connected for both prey and predator. Presence and absence of predator dispersal was cross-classified with low and high connectivity. The effect of connectivity on local and regional richness strongly depended on whether corridors were open for the predator. Local richness was initially positively affected by connectivity through rescue of species from stochastic extinctions. With predator dispersal, however, this positive effect soon turned negative as the predator spread over the metacommunity. Regional richness was unaffected by connectivity when local communities were connected only for the prey, while predator dispersal resulted in a pronounced decrease of regional richness. The level of connectivity influenced the speed of richness decline, with regional species extinctions being delayed for one week in weakly connected metacommunities. While connectivity enabled rescue of prey species from stochastic extinctions, deterministic extinctions due to predation were not overcome through reimmigration from predator-free refuges. Prey reimmigrating into these sink habitats appeared to be directly converted into increased predator abundance. Connectivity thus had a positive effect on the predator, even when the predator was not dispersing itself. Our study illustrates that dispersal of a species with strong negative effects on other community members shapes the dispersal-diversity relationship. When connections enable the spread of a generalist predator, positive effects of connectivity on prey species richness are outweighed by regional extinctions through predation

Avian cholera, a threat to the viability of an Arctic seabird colony?

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 7 (2012): e29659, doi:10.1371/journal.pone.0029659.Evidence that infectious diseases cause wildlife population extirpation or extinction remains anecdotal and it is unclear whether the impacts of a pathogen at the individual level can scale up to population level so drastically. Here, we quantify the response of a Common eider colony to emerging epidemics of avian cholera, one of the most important infectious diseases affecting wild waterfowl. We show that avian cholera has the potential to drive colony extinction, even over a very short period. Extinction depends on disease severity (the impact of the disease on adult female survival) and disease frequency (the number of annual epidemics per decade). In case of epidemics of high severity (i.e., causing >30% mortality of breeding females), more than one outbreak per decade will be unsustainable for the colony and will likely lead to extinction within the next century; more than four outbreaks per decade will drive extinction to within 20 years. Such severity and frequency of avian cholera are already observed, and avian cholera might thus represent a significant threat to viability of breeding populations. However, this will depend on the mechanisms underlying avian cholera transmission, maintenance, and spread, which are currently only poorly known.The study was supported by the Canadian Wildlife Service-Environment Canada (http://www.ec.gc.ca/), Nunavut Wildlife Management Board (http:// www.nwmb.com/), Greenland Institute of Natural Resources (http://www.natur.gl/), Polar Continental Shelf Project (http://polar.nrcan.gc.ca/), Fonds Que´be´cois de la Recherche sur la Nature et les Technologies (http://www.fqrnt.gouv.qc.ca/), Canadian Network of Centres of Excellence ArcticNet (http://www.arcticnet.ulaval. ca/), Natural Sciences and Engineering Research Council of Canada (http://www.nserc-crsng.gc.ca/), and the Department of Indian Affairs and Northern Canada (http://www.ainc-inac.gc.ca/)

The quality of reporting in cluster randomised crossover trials: proposal for reporting items and an assessment of reporting quality

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.SA was supported in part by a Monash University Graduate Scholarship and a National Health and Medical Research Council of Australia Centre of Research Excellence grant (1035261) to the Victorian Centre for Biostatistics (ViCBiostat). Funding was provided to KM through a National Institute for Health Research (NIHR) research methods fellowship (MET-12-16). JM was supported by a National Health and Medical Research Council (NHMRC) Australian Public Health Fellowship (1072366)

Exercise augmentation compared to usual care for Post Traumatic Stress Disorder: A Randomised Controlled Trial (The REAP study: Randomised Exercise Augmentation for PTSD)

<p>Abstract</p> <p>Background</p> <p>The physical wellbeing of people with mental health conditions can often be overlooked in order to treat the primary mental health condition as a priority. Exercise however, can potentially improve both the primary psychiatric condition as well as physical measures that indicate risk of other conditions such as diabetes mellitus and cardiovascular disease. Evidence supports the role of exercise as an important component of treatment for depression and anxiety, yet no randomised controlled trials (RCT's) have been conducted to evaluate the use of exercise in the treatment of people with post traumatic stress disorder (PTSD).</p> <p>This RCT will investigate the effects of structured, progressive exercise on PTSD symptoms, functional ability, body composition, physical activity levels, sleep patterns and medication usage.</p> <p>Methods and design</p> <p>Eighty participants with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of PTSD will be recruited. Participants will have no contraindications to exercise and will be cognitively able to provide consent to participate in the study.</p> <p>The primary outcome measures will be PTSD symptoms, measured through the PTSD Checklist Civilian (PCL-C) scale. Secondary outcome measures will assess depression and anxiety, mobility and strength, body composition, physical activity levels, sleep patterns and medication usage. All outcomes will be assessed by a health or exercise professional masked to group allocation at baseline and 12 weeks after randomisation.</p> <p>The intervention will be a 12 week individualised program, primarily involving resistance exercises with the use of exercise bands. A walking component will also be incorporated. Participants will complete one supervised session per week, and will be asked to perform at least two other non-supervised exercise sessions per week. Both intervention and control groups will receive all usual non-exercise interventions including psychotherapy, pharmaceutical interventions and group therapy.</p> <p>Discussion</p> <p>This study will determine the effect of an individualised and progressive exercise intervention on PTSD symptoms, depression and anxiety, mobility and strength, body composition, physical activity levels, sleep patterns and medication usage among people with a DSM-IV diagnosis of PTSD.</p> <p>Trial Registration</p> <p><a href="http://www.anzctr.org.au/ACTRN12605000567628.aspx">ACTRN12610000579099</a></p

Dementia and Physical Activity (DAPA) - an exercise intervention to improve cognition in people with mild to moderate dementia: Study protocol for a randomized controlled trial

Background: Dementia is more common in older than in younger people, and as a result of the ageing of the population in developed countries, it is becoming more prevalent. Drug treatments for dementia are limited, and the main support offered to people with dementia and their families is generally services to mitigate against loss of function. Physical exercise is a candidate non-pharmacological treatment for dementia. Methods/Design: DAPA is a randomised controlled trial funded by the National Institute for Health Research Health Technology Assessment programme to estimate the effect of a 4-month, moderate- to hard-intensity exercise training programme and subsequent advice to remain active, on cognition (primary outcome) at 12 months in people with mild to moderate dementia. Community-dwelling participants (with their carers where possible), who are able to walk 3 metres without human assistance, able to undertake an exercise programme and do not have any unstable or terminal illness are recruited. Participants are then randomised by an independent statistician using a computerised random number generator to usual care or exercise at a 2:1 ratio in favour of exercise. The exercise intervention comprises 29, 1-hour-long exercise classes, run twice weekly at suitable venues such as leisure centres, which include aerobic exercise (on static bikes) and resistance exercise (using weights). Goals for independent exercise are set while the classes are still running, and supported thereafter with phone calls. The primary outcome is measured using ADAS-cog. Secondary outcome measures include behavioural symptoms, functional ability, quality of life and carer burden. Primary and secondary outcomes will be measured at baseline and at 6 and 12 months after randomisation, by researchers masked to participant randomisation in the participants' own homes. An economic evaluation will be carried out in parallel to the RCT, as will a qualitative study capturing the experiences of participants, carers and staff delivering the intervention. Discussion: The DAPA study will be the first large, randomised trial of the cognitive effects of exercise on people with dementia. The intervention is designed to be capable of being delivered within the constraints of NHS service provision, and the economic evaluation will allow assessment of its cost-effectiveness. Trial registration: DAPA was registered with the ISRCTN database on 29 July 2011, registration number ISRCTN32612072. © 2016 Atherton et al

STAT3 Is Activated by JAK2 Independent of Key Oncogenic Driver Mutations in Non-Small Cell Lung Carcinoma

Constitutive activation of STAT3 is a common feature in many solid tumors including non-small cell lung carcinoma (NSCLC). While activation of STAT3 is commonly achieved by somatic mutations to JAK2 in hematologic malignancies, similar mutations are not often found in solid tumors. Previous work has instead suggested that STAT3 activation in solid tumors is more commonly induced by hyperactive growth factor receptors or autocrine cytokine signaling. The interplay between STAT3 activation and other well-characterized oncogenic “driver” mutations in NSCLC has not been fully characterized, though constitutive STAT3 activation has been proposed to play an important role in resistance to various small-molecule therapies that target these oncogenes. In this study we demonstrate that STAT3 is constitutively activated in human NSCLC samples and in a variety of NSCLC lines independent of activating KRAS or tyrosine kinase mutations. We further show that genetic or pharmacologic inhibition of the gp130/JAK2 signaling pathway disrupts activation of STAT3. Interestingly, treatment of NSCLC cells with the JAK1/2 inhibitor ruxolitinib has no effect on cell proliferation and viability in two-dimensional culture, but inhibits growth in soft agar and xenograft assays. These data demonstrate that JAK2/STAT3 signaling operates independent of known driver mutations in NSCLC and plays critical roles in tumor cell behavior that may not be effectively inhibited by drugs that selectively target these driver mutations

Positive and Negative Regulation of Gli Activity by Kif7 in the Zebrafish Embryo

Loss of function mutations of Kif7, the vertebrate orthologue of the Drosophila Hh pathway component Costal2, cause defects in the limbs and neural tubes of mice, attributable to ectopic expression of Hh target genes. While this implies a functional conservation of Cos2 and Kif7 between flies and vertebrates, the association of Kif7 with the primary cilium, an organelle absent from most Drosophila cells, suggests their mechanisms of action may have diverged. Here, using mutant alleles induced by Zinc Finger Nuclease-mediated targeted mutagenesis, we show that in zebrafish, Kif7 acts principally to suppress the activity of the Gli1 transcription factor. Notably, we find that endogenous Kif7 protein accumulates not only in the primary cilium, as previously observed in mammalian cells, but also in cytoplasmic puncta that disperse in response to Hh pathway activation. Moreover, we show that Drosophila Costal2 can substitute for Kif7, suggesting a conserved mode of action of the two proteins. We show that Kif7 interacts with both Gli1 and Gli2a and suggest that it functions to sequester Gli proteins in the cytoplasm, in a manner analogous to the regulation of Ci by Cos2 in Drosophila. We also show that zebrafish Kif7 potentiates Gli2a activity by promoting its dissociation from the Suppressor of Fused (Sufu) protein and present evidence that it mediates a Smo dependent modification of the full length form of Gli2a. Surprisingly, the function of Kif7 in the zebrafish embryo appears restricted principally to mesodermal derivatives, its inactivation having little effect on neural tube patterning, even when Sufu protein levels are depleted. Remarkably, zebrafish lacking all Kif7 function are viable, in contrast to the peri-natal lethality of mouse kif7 mutants but similar to some Acrocallosal or Joubert syndrome patients who are homozygous for loss of function KIF7 alleles

Biogeographical Survey Identifies Consistent Alternative Physiological Optima and a Minor Role for Environmental Drivers in Maintaining a Polymorphism

The contribution of adaptive mechanisms in maintaining genetic polymorphisms is still debated in many systems. To understand the contribution of selective factors in maintaining polymorphism, we investigated large-scale (>1000 km) geographic variation in morph frequencies and fitness-related physiological traits in the damselfly Nehalennia irene. As fitness-related physiological traits, we investigated investment in immune function (phenoloxidase activity), energy storage and fecundity (abdomen protein and lipid content), and flight muscles (thorax protein content). In the first part of the study, our aim was to identify selective agents maintaining the large-scale spatial variation in morph frequencies. Morph frequencies varied considerably among populations, but, in contrast to expectation, in a geographically unstructured way. Furthermore, frequencies co-varied only weakly with the numerous investigated ecological parameters. This suggests that spatial frequency patterns are driven by stochastic processes, or alternatively, are consequence of highly variable and currently unidentified ecological conditions. In line with this, the investigated ecological parameters did not affect the fitness-related physiological traits differently in both morphs. In the second part of the study, we aimed at identifying trade-offs between fitness-related physiological traits that may contribute to the local maintenance of both colour morphs by defining alternative phenotypic optima, and test the spatial consistency of such trade-off patterns. The female morph with higher levels of phenoloxidase activity had a lower thorax protein content, and vice versa, suggesting a trade-off between investments in immune function and in flight muscles. This physiological trade-off was consistent across the geographical scale studied and supports widespread correlational selection, possibly driven by male harassment, favouring alternative trait combinations in both female morphs