Autocrine inhibition of cell motility can drive epithelial branching morphogenesis in the absence of growth

Epithelial branching morphogenesis drives the development of organs such as the lung, salivary gland, kidney and the mammary gland. It involves cell proliferation, cell differentiation and cell migration. An elaborate network of chemical and mechanical signals between the epithelium and the surrounding mesenchymal tissues regulates the formation and growth of branching organs. Surprisingly, when cultured in isolation from mesenchymal tissues, many epithelial tissues retain the ability to exhibit branching morphogenesis even in the absence of proliferation. In this work, we propose a simple, experimentally plausible mechanism that can drive branching morphogenesis in the absence of proliferation and cross-talk with the surrounding mesenchymal tissue. The assumptions of our mathematical model derive from in vitro observations of the behaviour of mammary epithelial cells. These data show that autocrine secretion of the growth factor TGFβ1 inhibits the formation of cell protrusions, leading to curvature-dependent inhibition of sprouting. Our hybrid cellular Potts and partial-differential equation model correctly reproduces the experimentally observed tissue-geometry-dependent determination of the sites of branching, and it suffices for the formation of self-avoiding branching structures in the absence and also in the presence of cell proliferation. This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.</p

Availability of public goods shapes the evolution of competing metabolic strategies

Tradeoffs provide a rationale for the outcome of natural selection. A prominent example is the negative correlation between the growth rate and the biomass yield in unicellular organisms. This tradeoff leads to a dilemma, where the optimization of growth rate is advantageous for an individual, whereas the optimization of the biomass yield would be advantageous for a population. High-rate strategies are observed in a broad variety of organisms such as Escherichia coli, yeast, and cancer cells. Growth in suspension cultures favors fast-growing organisms, whereas spatial structure is of importance for the evolution of high-yield strategies. Despite this realization, experimental methods to directly select for increased yield are lacking. We here show that the serial propagation of a microbial population in a water-in-oil emulsion allows selection of strains with increased biomass yield. The propagation in emulsion creates a spatially structured environment where the growth-limiting substrate is privatized for populations founded by individual cells. Experimental evolution of several isogenic Lactococcus lactis strains demonstrated the existence of a tradeoff between growth rate and biomass yield as an apparent Pareto front. The underlying mutations altered glucose transport and led to major shifts between homofermentative and heterofermentative metabolism, accounting for the changes in metabolic efficiency. The results demonstrated the impact of privatizing a public good on the evolutionary outcome between competing metabolic strategies. The presented approach allows the investigation of fundamental questions in biology such as the evolution of cooperation, cell-cell interactions, and the relationships between environmental and metabolic constraints

First full-size ATLAS barrel toroid coil successfully tested up to 22 kA at 4 T

The Superconducting Barrel Toroid is providing (together with the two End-Cap Toroids not presented here) the magnetic field for the muon detectors in the ATLAS Experiment at the LHC at CERN. The toroid with outer dimensions of 25 m length and 20 m diameter, is built up from 8 identical racetrack coils. The coils with 120 turns each are wound with an aluminum stabilized NbTi conductor and operate at 20.5 kA at 3.9 T local field in the windings and is conduction cooled at 4.8 K by circulating forced flow helium in cooling tubes attached to the cold mass. The 8 coils of 25 m * 5 m are presently under construction and the first coils have already been fully integrated and tested. Meanwhile the assembly of the toroid 100 m underground in the ATLAS cavern at CERN has started. The 8 coils are individually tested on surface before installation. In this paper the test of the first coil, unique in size and manufacturing technology, is described in detail and the results are compared to the previous experience with the 9 m long B0 model coil

The ATLAS Experiment at the CERN Large Hadron Collider

The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented