Mobility promotes and jeopardizes biodiversity in rock-paper-scissors games

Biodiversity is essential to the viability of ecological systems. Species diversity in ecosystems is promoted by cyclic, non-hierarchical interactions among competing populations. Such non-transitive relations lead to an evolution with central features represented by the `rock-paper-scissors' game, where rock crushes scissors, scissors cut paper, and paper wraps rock. In combination with spatial dispersal of static populations, this type of competition results in the stable coexistence of all species and the long-term maintenance of biodiversity. However, population mobility is a central feature of real ecosystems: animals migrate, bacteria run and tumble. Here, we observe a critical influence of mobility on species diversity. When mobility exceeds a certain value, biodiversity is jeopardized and lost. In contrast, below this critical threshold all subpopulations coexist and an entanglement of travelling spiral waves forms in the course of temporal evolution. We establish that this phenomenon is robust, it does not depend on the details of cyclic competition or spatial environment. These findings have important implications for maintenance and evolution of ecological systems and are relevant for the formation and propagation of patterns in excitable media, such as chemical kinetics or epidemic outbreaks.Comment: Final submitted version; the printed version can be found at http://dx.doi.org/10.1038/nature06095 Supplementary movies are available at http://www.theorie.physik.uni-muenchen.de/lsfrey/images_content/movie1.AVI and http://www.theorie.physik.uni-muenchen.de/lsfrey/images_content/movie2.AV

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Mass extinctions drove increased global faunal cosmopolitanism on the supercontinent Pangaea

Mass extinctions have profoundly impacted the evolution of life through not only reducing taxonomic diversity but also reshaping ecosystems and biogeographic patterns. In particular, they are considered to have driven increased biogeographic cosmopolitanism, but quantitative tests of this hypothesis are rare and have not explicitly incorporated information on evolutionary relationships. Here we quantify faunal cosmopolitanism using a phylogenetic network approach for 891 terrestrial vertebrate species spanning the late Permian through Early Jurassic. This key interval witnessed the Permian–Triassic and Triassic–Jurassic mass extinctions, the onset of fragmentation of the supercontinent Pangaea, and the origins of dinosaurs and many modern vertebrate groups. Our results recover significant increases in global faunal cosmopolitanism following both mass extinctions, driven mainly by new, widespread taxa, leading to homogenous ‘disaster faunas’. Cosmopolitanism subsequently declines in post-recovery communities. These shared patterns in both biotic crises suggest that mass extinctions have predictable influences on animal distribution and may shed light on biodiversity loss in extant ecosystems

Dinosaurs reveal the geographical signature of an evolutionary radiation

Dinosaurs dominated terrestrial ecosystems across the globe for over 100 million years and provide a classic example of an evolutionary radiation. However, little is known about how these animals radiated geographically to become globally distributed. Here, we use a biogeographical model to reconstruct the dinosaurs’ ancestral locations, revealing the spatial mechanisms that underpinned this 170-million-year-long radiation. We find that dinosaurs spread rapidly initially, followed by a significant continuous and gradual reduction in their speed of movement towards the Cretaceous/Tertiary boundary (66 million years ago). This suggests that the predominant mode of dinosaur speciation changed through time with speciation originally largely driven by geographical isolation—when dinosaurs speciated more, they moved further. This was gradually replaced by increasing levels of sympatric speciation (species taking advantage of ecological opportunities within their existing environment) as terrestrial space became a limiting factor. Our results uncover the geographical signature of an evolutionary radiation

Transphyletic conservation of developmental regulatory state in animal evolution

Specific regulatory states, i.e., sets of expressed transcription factors, define the gene expression capabilities of cells in animal development. Here we explore the functional significance of an unprecedented example of regulatory state conservation from the cnidarian Nematostella to Drosophila, sea urchin, fish, and mammals. Our probe is a deeply conserved cis-regulatory DNA module of the SRY-box B2 (soxB2), recognizable at the sequence level across many phyla. Transphyletic cis-regulatory DNA transfer experiments reveal that the plesiomorphic control function of this module may have been to respond to a regulatory state associated with neuronal differentiation. By introducing expression constructs driven by this module from any phyletic source into the genomes of diverse developing animals, we discover that the regulatory state to which it responds is used at different levels of the neurogenic developmental process, including patterning and development of the vertebrate forebrain and neurogenesis in the Drosophila optic lobe and brain. The regulatory state recognized by the conserved DNA sequence may have been redeployed to different levels of the developmental regulatory program during evolution of complex central nervous systems

Induction of Larval Metamorphosis of the Coral Acropora millepora by Tetrabromopyrrole Isolated from a Pseudoalteromonas Bacterium

The induction of larval attachment and metamorphosis of benthic marine invertebrates is widely considered to rely on habitat specific cues. While microbial biofilms on marine hard substrates have received considerable attention as specific signals for a wide and phylogenetically diverse array of marine invertebrates, the presumed chemical settlement signals produced by the bacteria have to date not been characterized. Here we isolated and fully characterized the first chemical signal from bacteria that induced larval metamorphosis of acroporid coral larvae (Acropora millepora). The metamorphic cue was identified as tetrabromopyrrole (TBP) in four bacterial Pseudoalteromonas strains among a culture library of 225 isolates obtained from the crustose coralline algae Neogoniolithon fosliei and Hydrolithon onkodes. Coral planulae transformed into fully developed polyps within 6 h, but only a small proportion of these polyps attached to the substratum. The biofilm cell density of the four bacterial strains had no influence on the ratio of attached vs. non-attached polyps. Larval bioassays with ethanolic extracts of the bacterial isolates, as well as synthetic TBP resulted in consistent responses of coral planulae to various doses of TBP. The lowest bacterial density of one of the Pseudoalteromonas strains which induced metamorphosis was 7,000 cells mm−2 in laboratory assays, which is on the order of 0.1 –1% of the total numbers of bacteria typically found on such surfaces. These results, in which an actual cue from bacteria has been characterized for the first time, contribute significantly towards understanding the complex process of acroporid coral larval settlement mediated through epibiotic microbial biofilms on crustose coralline algae

In-Vivo Biodistribution and Safety of 99mTc-LLP2A-HYNIC in Canine Non-Hodgkin Lymphoma

Theranostic agents are critical for improving the diagnosis and treatment of non-Hodgkin Lymphoma (NHL). The peptidomimetic LLP2A is a novel peptide receptor radiotherapy candidate for treating NHL that expresses the activated α4β1 integrin. Tumor-bearing dogs are an excellent model of human NHL with similar clinical characteristics, behavior, and compressed clinical course. Canine in vivo imaging studies will provide valuable biodistribution and affinity information that reflects a diverse clinical population of lymphoma. This may also help to determine potential dose-limiting radiotoxicity to organs in human clinical trials. To validate this construct in a naturally occurring model of NHL, we performed in-vivo molecular targeted imaging and biodistribution in 3 normal dogs and 5 NHL bearing dogs. 99mTc-LLP2A-HYNIC-PEG and 99mTc-LLP2A-HYNIC were successfully synthesized and had very good labeling efficiency and radiochemical purity. 99mTc-LLP2A-HYNIC and 99mTc-LLP2A-HYNIC-PEG had biodistribution in keeping with their molecular size, with 99mTc-LLP2A-HYNIC-PEG remaining longer in the circulation, having higher tissue uptake, and having more activity in the liver compared to 99mTc-LLP2A-HYNIC. 99mTc-LLP2A-HYNIC was mainly eliminated through the kidneys with some residual activity. Radioactivity was reduced to near-background levels at 6 hours after injection. In NHL dogs, tumor showed moderately increased activity over background, with tumor activity in B-cell lymphoma dogs decreasing after chemotherapy. This compound is promising in the development of targeted drug-delivery radiopharmaceuticals and may contribute to translational work in people affected by non-Hodgkin lymphoma

Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation

<p>Abstract</p> <p>Background</p> <p>Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties. Therapeutic activity, as well as toxicity and other essential properties can be analysed and optimized simultaneously, independently of one another. Such methodology is suitable for a search of novel, non-toxic, active anti-malarial compounds.</p> <p>Methods</p> <p>A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and <it>de novo </it>molecular design.</p> <p>Results</p> <p>Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were discovered and experimentally validated. Twelve compounds were identified <it>in silico </it>and tested <it>in vitro</it>; eight of them showed anti-malarial activity (IC50 ≤ 10 μM), with six being very effective (IC50 ≤ 1 μM), and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a therapeutic index of more than 6,900 for the most active compound.</p> <p>Conclusions</p> <p>Gradient's metric modelling approach and electron-density molecular representations can be powerful tools in the discovery and design of novel anti-malarial compounds. Since the quantum models are agnostic of the particular biological target, the technology can account for different mechanisms of action and be used for <it>de novo </it>design of small molecules with activity against not only the asexual phase of the malaria parasite, but also against the liver stage of the parasite development, which may lead to true causal prophylaxis.</p

Stabilizing Salt-Bridge Enhances Protein Thermostability by Reducing the Heat Capacity Change of Unfolding

Most thermophilic proteins tend to have more salt bridges, and achieve higher thermostability by up-shifting and broadening their protein stability curves. While the stabilizing effect of salt-bridge has been extensively studied, experimental data on how salt-bridge influences protein stability curves are scarce. Here, we used double mutant cycles to determine the temperature-dependency of the pair-wise interaction energy and the contribution of salt-bridges to ΔCp in a thermophilic ribosomal protein L30e. Our results showed that the pair-wise interaction energies for the salt-bridges E6/R92 and E62/K46 were stabilizing and insensitive to temperature changes from 298 to 348 K. On the other hand, the pair-wise interaction energies between the control long-range ion-pair of E90/R92 were negligible. The ΔCp of all single and double mutants were determined by Gibbs-Helmholtz and Kirchhoff analyses. We showed that the two stabilizing salt-bridges contributed to a reduction of ΔCp by 0.8–1.0 kJ mol−1 K−1. Taken together, our results suggest that the extra salt-bridges found in thermophilic proteins enhance the thermostability of proteins by reducing ΔCp, leading to the up-shifting and broadening of the protein stability curves

Paleodistributions and Comparative Molecular Phylogeography of Leafcutter Ants (Atta spp.) Provide New Insight into the Origins of Amazonian Diversity

The evolutionary basis for high species diversity in tropical regions of the world remains unresolved. Much research has focused on the biogeography of speciation in the Amazon Basin, which harbors the greatest diversity of terrestrial life. The leading hypotheses on allopatric diversification of Amazonian taxa are the Pleistocene refugia, marine incursion, and riverine barrier hypotheses. Recent advances in the fields of phylogeography and species-distribution modeling permit a modern re-evaluation of these hypotheses. Our approach combines comparative, molecular phylogeographic analyses using mitochondrial DNA sequence data with paleodistribution modeling of species ranges at the last glacial maximum (LGM) to test these hypotheses for three co-distributed species of leafcutter ants (Atta spp.). The cumulative results of all tests reject every prediction of the riverine barrier hypothesis, but are unable to reject several predictions of the Pleistocene refugia and marine incursion hypotheses. Coalescent dating analyses suggest that population structure formed recently (Pleistocene-Pliocene), but are unable to reject the possibility that Miocene events may be responsible for structuring populations in two of the three species examined. The available data therefore suggest that either marine incursions in the Miocene or climate changes during the Pleistocene—or both—have shaped the population structure of the three species examined. Our results also reconceptualize the traditional Pleistocene refugia hypothesis, and offer a novel framework for future research into the area