Evolution at the edge of expanding populations

Predicting evolution of expanding populations is critical to control biological threats such as invasive species and cancer metastasis. Expansion is primarily driven by reproduction and dispersal, but nature abounds with examples of evolution where organisms pay a reproductive cost to disperse faster. When does selection favor this 'survival of the fastest?' We searched for a simple rule, motivated by evolution experiments where swarming bacteria evolved into an hyperswarmer mutant which disperses $\sim 100\%$ faster but pays a growth cost of $\sim 10 \%$ to make many copies of its flagellum. We analyzed a two-species model based on the Fisher equation to explain this observation: the population expansion rate ($v$) results from an interplay of growth ($r$) and dispersal ($D$) and is independent of the carrying capacity: $v=2\sqrt{rD}$. A mutant can take over the edge only if its expansion rate ($v_2$) exceeds the expansion rate of the established species ($v_1$); this simple condition ($v_2 > v_1$) determines the maximum cost in slower growth that a faster mutant can pay and still be able to take over. Numerical simulations and time-course experiments where we tracked evolution by imaging bacteria suggest that our findings are general: less favorable conditions delay but do not entirely prevent the success of the fastest. Thus, the expansion rate defines a traveling wave fitness, which could be combined with trade-offs to predict evolution of expanding populations

MYC is a metastasis gene for non-small-cell lung cancer.

Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. NSCLC is the most lethal human cancer due to its high rate of metastasis. Lack of a suitable animal model has so far hampered analysis of metastatic progression. We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c-MYC alone induced frank tumor growth only after long latency at which time secondary mutations in K-Ras or LKB1 were detected reminiscent of human NSCLC. Combination with C-RAF led to immediate acceleration of tumor growth, conversion to papillary epithelial cells and angiogenic switch induction. Moreover, addition of c-MYC was sufficient to induce macrometastasis in liver and lymph nodes with short latency associated with lineage switch events. Thus we have generated the first conditional model for metastasis of NSCLC and identified a gene, c-MYC that is able to orchestrate all steps of this process. Potential markers for detection of metastasis were identified and validated for diagnosis of human biopsies. These markers may represent targets for future therapeutic intervention as they include genes such as Gata4 that are exclusively expressed during lung development

Spatially hybrid computations for streamer discharges with generic features of pulled fronts: I. Planar fronts

Streamers are the first stage of sparks and lightning; they grow due to a strongly enhanced electric field at their tips; this field is created by a thin curved space charge layer. These multiple scales are already challenging when the electrons are approximated by densities. However, electron density fluctuations in the leading edge of the front and non-thermal stretched tails of the electron energy distribution (as a cause of X-ray emissions) require a particle model to follow the electron motion. As super-particle methods create wrong statistics and numerical artifacts, modeling the individual electron dynamics in streamers is limited to early stages where the total electron number still is limited. The method of choice is a hybrid computation in space where individual electrons are followed in the region of high electric field and low density while the bulk of the electrons is approximated by densities (or fluids). We here develop the hybrid coupling for planar fronts. First, to obtain a consistent flux at the interface between particle and fluid model in the hybrid computation, the widely used classical fluid model is replaced by an extended fluid model. Then the coupling algorithm and the numerical implementation of the spatially hybrid model are presented in detail, in particular, the position of the model interface and the construction of the buffer region. The method carries generic features of pulled fronts that can be applied to similar problems like large deviations in the leading edge of population fronts etc.Comment: 33 pages, 15 figures and 2 table

Topographic effects on dispersal patterns of Phytophthora cinnamomi at a stand scale in a Spanish heathland

Phytophthora cinnamomi es uno de los patógenos de plantas más importantes del mundo, causando la putrefacción de las raíces en más de mil especies de plantas. Este estudio de observación se llevó a cabo en un brezal infectado con P. cinnamomi de Erica umbellata utilizado como pasto para cabras. Los patrones y formas de los focos de la enfermedad y su distribución se describieron en un contexto espacial y temporal mediante un registro de fotografías aéreas. Se seleccionó un conjunto de rasgos topográficos sobre la base de una hipótesis de dinámica de la enfermedad y se analizaron sus efectos en los patrones espaciales de la enfermedad observados. Las infecciones incipientes situadas en terreno llano se expandieron como patrones de frente circular compacto con una baja tasa de crecimiento. En las laderas, los parches de la enfermedad se desarrollaron más rápidamente en la pendiente, formando formas parabólicas. La dirección del eje de las parábolas estaba altamente correlacionada con el aspecto del terreno, mientras que la amplitud parabólica se asociaba con la curvatura y la pendiente del terreno. Con el paso de los años aparecieron nuevos focos secundarios que produjeron un aumento acelerado de la superficie afectada. Estos nuevos focos se observaron en sitios donde la densidad de la enfermedad era mayor o cerca de sitios más frecuentemente visitados por animales como el establo o el cultivo de forraje. Por el contrario, un menor número de focos de enfermedad se producen en zonas que los animales son reacios a visitar, por ejemplo, donde tienen un corto alcance de visión. Nuestros resultados sugieren que 1) el crecimiento de los focos existentes de P. cinnamomi se controla mediante una combinación de contacto de raíz a raíz y flujos de agua, 2) el aumento del área enferma surge principalmente de la multiplicación de parches, 3) la formación de nuevos focos está mediada por el transporte a larga distancia debido al movimiento de animales y humanos a lo largo de ciertas rutas preferenciales, y 4) los rasgos de geomorfología y topografía están asociados con la epidemiología de este patógeno transmitido por el suelo.Phytophthora cinnamomi is one of the most important plant pathogens in the world, causing root rot in more than a thousand plant species. This observational study was carried out on a P. cinnamomi infected heathland of Erica umbellata used as goat pasture. The patterns and shapes of disease foci and their distribution were described in a spatial and temporal context using an aerial photograph record. A set of topographic traits was selected on the basis of a disease dynamic hypothesis and their effects on observed spatial disease patterns were analyzed. Incipient infections situated in flat terrain expanded as compact circular front patterns with a low growth rate. On slopes, disease patches developed more rapidly down slope, forming parabolic shapes. The axis direction of the parabolas was highly correlated with terrain aspect, while the parabolic amplitude was associated with land curvature and slope. New secondary foci appeared over the years producing an accelerated increase of the affected surface. These new foci were observed in sites where disease density was higher or near sites more frequently visited by animals such as the stable or the forage crop. In contrast, a smaller number of disease foci occur in areas which animals are reluctant to visit, such as where they have a short range of vision. Our results suggest that 1) the growth of existing P. cinnamomi foci is controlled by a combination of root-to-root contact and wáter flows, 2) the increase in the diseased area arises mainly from the multiplication of patches, 3) the formation of new foci is mediated by long-distance transport due to the movement of animals and humans along certain preferential pathways, and 4) geomorphology and topography traits are associated with the epidemiology of this soil-borne pathogen.• Gobierno de Extremadura. Ayuda • Ministerio de Economía y Competitividad. Proyecto FIS2016-76359-P, para Enrique Alfonso Abad JarillopeerReviewe

In vivo analysis of the role of tenascin-C in tumorigenesis

The extracellular matrix molecule tenascin-C (TNC) is an important factor in tumor progression. In the multistage carcinogenesis Rip1Tag2 (RT2) model, in which the SV40 T antigen induces stochastically non-metastatic insulinomas we determined how ectopically expressed human TNC affects tumor progression. Transgenic RipTNC mice with rat insulin promoter driven ectopic expression of TNC in the pancreatic β-cells were generated. RipTNC mice did not exhibit detectable alterations in pancreas morphology and function, but displayed enhanced angiogenesis. A direct angiogenesis-promoting effect was demonstrated by purified TNC in the chicken chorioallantoic membrane assay. Upon crossing into the RT2 background enhanced tumor cell proliferation and increased angiogenesis with strong hemorrhages was detected in tumors of double transgenic RT2/TNC mice. Ectopically expressed TNC accelerated carcinoma progression with nuclear translocation of β-catenin. Nuclear translocation of β-catenin occurred also in MCF7 breast cancer cells in which TNC induced EMT. RT2/TNC tumor cells accumulated in tubes made of TNC and laminin that were not lined by endothelial cells. In contrast to RT2 mice, RT2/TNC littermates developed local lymph node and distant liver metastasis. In conclusion, in this first tumorigenesis model mimicking ectopic expression of TNC in cancer, TNC induced nuclear translocation of β-catenin that can explain TNC-driven angiogenesis, tumor cell proliferation, invasion and metastasis which may involve tumor cell dissemination by the TNC-containing tubes