Paracrine Behaviors Arbitrate Parasite-Like Interactions Between Tumor Subclones.

Explaining the emergence and maintenance of intratumor heterogeneity is an important question in cancer biology. Tumor cells can generate considerable subclonal diversity, which influences tumor growth rate, treatment resistance, and metastasis, yet we know remarkably little about how cells from different subclones interact. Here, we confronted two murine mammary cancer cell lines to determine both the nature and mechanisms of subclonal cellular interactions in vitro. Surprisingly, we found that, compared to monoculture, growth of the "winner" was enhanced by the presence of the "loser" cell line, whereas growth of the latter was reduced. Mathematical modeling and laboratory assays indicated that these interactions are mediated by the production of paracrine metabolites resulting in the winner subclone effectively "farming" the loser. Our findings add a new level of complexity to the mechanisms underlying subclonal growth dynamics.

A framework for how environment contributes to cancer risk.

Evolutionary theory explains why metazoan species are largely protected against the negative fitness effects of cancers. Nevertheless, cancer is often observed at high incidence across a range of species. Although there are many challenges to quantifying cancer epidemiology and assessing its causes, we claim that most modern-day cancer in animals - and humans in particular - are due to environments deviating from central tendencies of distributions that have prevailed during cancer resistance evolution. Such novel environmental conditions may be natural and/or of anthropogenic origin, and may interface with cancer risk in numerous ways, broadly classifiable as those: increasing organism body size and/or life span, disrupting processes within the organism, and affecting germline. We argue that anthropogenic influences, in particular, explain much of the present-day cancer risk across life, including in humans. Based on a literature survey of animal species and a parameterised mathematical model for humans, we suggest that combined risks of all cancers in a population beyond c. 5% can be explained to some extent by the influence of novel environments. Our framework provides a basis for understanding how natural environmental variation and human activity impact cancer risk, with potential implications for species ecology.

Antibiotic stress selects against cooperation in the pathogenic bacterium Pseudomonas aeruginosa.

Cheats are a pervasive threat to public goods production in natural and human communities, as they benefit from the commons without contributing to it. Although ecological antagonisms such as predation, parasitism, competition, and abiotic environmental stress play key roles in shaping population biology, it is unknown how such stresses generally affect the ability of cheats to undermine cooperation. We used theory and experiments to address this question in the pathogenic bacterium, Pseudomonas aeruginosa Although public goods producers were selected against in all populations, our competition experiments showed that antibiotics significantly increased the advantage of nonproducers. Moreover, the dominance of nonproducers in mixed cultures was associated with higher resistance to antibiotics than in either monoculture. Mathematical modeling indicates that accentuated costs to producer phenotypes underlie the observed patterns. Mathematical analysis further shows how these patterns should generalize to other taxa with public goods behaviors. Our findings suggest that explaining the maintenance of cooperative public goods behaviors in certain natural systems will be more challenging than previously thought. Our results also have specific implications for the control of pathogenic bacteria using antibiotics and for understanding natural bacterial ecosystems, where subinhibitory concentrations of antimicrobials frequently occur.

Inductive and electrostatic acceleration in relativistic jet-plasma interactions.

We report on the observation of rapid particle acceleration in numerical simulations of relativistic jet-plasma interactions and discuss the underlying mechanisms. The dynamics of a charge-neutral, narrow, electron-positron jet propagating through an unmagnetized electron-ion plasma was investigated using a three-dimensional, electromagnetic, particle-in-cell computer code. The interaction excited magnetic filamentation as well as electrostatic plasma instabilities. In some cases, the longitudinal electric fields generated inductively and electrostatically reached the cold plasma-wave-breaking limit, and the longitudinal momentum of about half the positrons increased by 50% with a maximum gain exceeding a factor of 2 during the simulation period. Particle acceleration via these mechanisms occurred when the criteria for Weibel instability were satisfied.