@article{1244, abstract = {Cell polarity refers to a functional spatial organization of proteins that is crucial for the control of essential cellular processes such as growth and division. To establish polarity, cells rely on elaborate regulation networks that control the distribution of proteins at the cell membrane. In fission yeast cells, a microtubule-dependent network has been identified that polarizes the distribution of signaling proteins that restricts growth to cell ends and targets the cytokinetic machinery to the middle of the cell. Although many molecular components have been shown to play a role in this network, it remains unknown which molecular functionalities are minimally required to establish a polarized protein distribution in this system. Here we show that a membrane-binding protein fragment, which distributes homogeneously in wild-type fission yeast cells, can be made to concentrate at cell ends by attaching it to a cytoplasmic microtubule end-binding protein. This concentration results in a polarized pattern of chimera proteins with a spatial extension that is very reminiscent of natural polarity patterns in fission yeast. However, chimera levels fluctuate in response to microtubule dynamics, and disruption of microtubules leads to disappearance of the pattern. Numerical simulations confirm that the combined functionality of membrane anchoring and microtubule tip affinity is in principle sufficient to create polarized patterns. Our chimera protein may thus represent a simple molecular functionality that is able to polarize the membrane, onto which additional layers of molecular complexity may be built to provide the temporal robustness that is typical of natural polarity patterns.}, author = {Recouvreux, Pierre and Sokolowski, Thomas R and Grammoustianou, Aristea and Tenwolde, Pieter and Dogterom, Marileen}, journal = {PNAS}, number = {7}, pages = {1811 -- 1816}, publisher = {National Academy of Sciences}, title = {{Chimera proteins with affinity for membranes and microtubule tips polarize in the membrane of fission yeast cells}}, doi = {10.1073/pnas.1419248113}, volume = {113}, year = {2016}, } @article{1248, abstract = {Life depends as much on the flow of information as on the flow of energy. Here we review the many efforts to make this intuition precise. Starting with the building blocks of information theory, we explore examples where it has been possible to measure, directly, the flow of information in biological networks, or more generally where information-theoretic ideas have been used to guide the analysis of experiments. Systems of interest range from single molecules (the sequence diversity in families of proteins) to groups of organisms (the distribution of velocities in flocks of birds), and all scales in between. Many of these analyses are motivated by the idea that biological systems may have evolved to optimize the gathering and representation of information, and we review the experimental evidence for this optimization, again across a wide range of scales.}, author = {Tkacik, Gasper and Bialek, William}, journal = {Annual Review of Condensed Matter Physics}, pages = {89 -- 117}, publisher = {Annual Reviews}, title = {{Information processing in living systems}}, doi = {10.1146/annurev-conmatphys-031214-014803}, volume = {7}, year = {2016}, } @article{1260, abstract = {In this work, the Gardner problem of inferring interactions and fields for an Ising neural network from given patterns under a local stability hypothesis is addressed under a dual perspective. By means of duality arguments, an integer linear system is defined whose solution space is the dual of the Gardner space and whose solutions represent mutually unstable patterns. We propose and discuss Monte Carlo methods in order to find and remove unstable patterns and uniformly sample the space of interactions thereafter. We illustrate the problem on a set of real data and perform ensemble calculation that shows how the emergence of phase dominated by unstable patterns can be triggered in a nonlinear discontinuous way.}, author = {De Martino, Daniele}, journal = {International Journal of Modern Physics C}, number = {6}, publisher = {World Scientific Publishing}, title = {{The dual of the space of interactions in neural network models}}, doi = {10.1142/S0129183116500674}, volume = {27}, year = {2016}, } @article{1266, abstract = {Cortical networks exhibit ‘global oscillations’, in which neural spike times are entrained to an underlying oscillatory rhythm, but where individual neurons fire irregularly, on only a fraction of cycles. While the network dynamics underlying global oscillations have been well characterised, their function is debated. Here, we show that such global oscillations are a direct consequence of optimal efficient coding in spiking networks with synaptic delays and noise. To avoid firing unnecessary spikes, neurons need to share information about the network state. Ideally, membrane potentials should be strongly correlated and reflect a ‘prediction error’ while the spikes themselves are uncorrelated and occur rarely. We show that the most efficient representation is when: (i) spike times are entrained to a global Gamma rhythm (implying a consistent representation of the error); but (ii) few neurons fire on each cycle (implying high efficiency), while (iii) excitation and inhibition are tightly balanced. This suggests that cortical networks exhibiting such dynamics are tuned to achieve a maximally efficient population code.}, author = {Chalk, Matthew J and Gutkin, Boris and Denève, Sophie}, journal = {eLife}, number = {2016JULY}, publisher = {eLife Sciences Publications}, title = {{Neural oscillations as a signature of efficient coding in the presence of synaptic delays}}, doi = {10.7554/eLife.13824}, volume = {5}, year = {2016}, } @article{1290, abstract = {We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline.}, author = {Stone, Laura and Baym, Michael and Lieberman, Tami and Chait, Remy P and Clardy, Jon and Kishony, Roy}, journal = {Nature Chemical Biology}, number = {11}, pages = {902 -- 904}, publisher = {Nature Publishing Group}, title = {{Compounds that select against the tetracycline-resistance efflux pump}}, doi = {10.1038/nchembio.2176}, volume = {12}, year = {2016}, } @inproceedings{1320, abstract = {In recent years, several biomolecular systems have been shown to be scale-invariant (SI), i.e. to show the same output dynamics when exposed to geometrically scaled input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant inputs. In this article, we show that SI systems-as well as systems invariant with respect to other input transformations-can realize nonlinear differential operators: when excited by inputs obeying functional forms characteristic for a given class of invariant systems, the systems' outputs converge to constant values directly quantifying the speed of the input.}, author = {Lang, Moritz and Sontag, Eduardo}, location = {Boston, MA, USA}, publisher = {IEEE}, title = {{Scale-invariant systems realize nonlinear differential operators}}, doi = {10.1109/ACC.2016.7526722}, volume = {2016-July}, year = {2016}, } @article{1332, abstract = {Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance.}, author = {Chait, Remy P and Palmer, Adam and Yelin, Idan and Kishony, Roy}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments}}, doi = {10.1038/ncomms10333}, volume = {7}, year = {2016}, } @article{1342, abstract = {A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, the microbial evolution and growth arena (MEGA)-plate, in which bacteria spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation of mutation and selection in a migrating bacterial front.While resistance increased consistently, multiple coexisting lineages diversified both phenotypically and genotypically. Analyzing mutants at and behind the propagating front,we found that evolution is not always led by the most resistant mutants; highly resistant mutants may be trapped behindmore sensitive lineages.TheMEGA-plate provides a versatile platformfor studying microbial adaption and directly visualizing evolutionary dynamics.}, author = {Baym, Michael and Lieberman, Tami and Kelsic, Eric and Chait, Remy P and Gross, Rotem and Yelin, Idan and Kishony, Roy}, journal = {Science}, number = {6304}, pages = {1147 -- 1151}, publisher = {American Association for the Advancement of Science}, title = {{Spatiotemporal microbial evolution on antibiotic landscapes}}, doi = {10.1126/science.aag0822}, volume = {353}, year = {2016}, } @article{1394, abstract = {The solution space of genome-scale models of cellular metabolism provides a map between physically viable flux configurations and cellular metabolic phenotypes described, at the most basic level, by the corresponding growth rates. By sampling the solution space of E. coliʼs metabolic network, we show that empirical growth rate distributions recently obtained in experiments at single-cell resolution can be explained in terms of a trade-off between the higher fitness of fast-growing phenotypes and the higher entropy of slow-growing ones. Based on this, we propose a minimal model for the evolution of a large bacterial population that captures this trade-off. The scaling relationships observed in experiments encode, in such frameworks, for the same distance from the maximum achievable growth rate, the same degree of growth rate maximization, and/or the same rate of phenotypic change. Being grounded on genome-scale metabolic network reconstructions, these results allow for multiple implications and extensions in spite of the underlying conceptual simplicity.}, author = {De Martino, Daniele and Capuani, Fabrizio and De Martino, Andrea}, journal = {Physical Biology}, number = {3}, publisher = {IOP Publishing Ltd.}, title = {{Growth against entropy in bacterial metabolism: the phenotypic trade-off behind empirical growth rate distributions in E. coli}}, doi = {10.1088/1478-3975/13/3/036005}, volume = {13}, year = {2016}, } @article{1420, abstract = {Selection, mutation, and random drift affect the dynamics of allele frequencies and consequently of quantitative traits. While the macroscopic dynamics of quantitative traits can be measured, the underlying allele frequencies are typically unobserved. Can we understand how the macroscopic observables evolve without following these microscopic processes? This problem has been studied previously by analogy with statistical mechanics: the allele frequency distribution at each time point is approximated by the stationary form, which maximizes entropy. We explore the limitations of this method when mutation is small (4Nμ < 1) so that populations are typically close to fixation, and we extend the theory in this regime to account for changes in mutation strength. We consider a single diallelic locus either under directional selection or with overdominance and then generalize to multiple unlinked biallelic loci with unequal effects. We find that the maximum-entropy approximation is remarkably accurate, even when mutation and selection change rapidly. }, author = {Bod'ová, Katarína and Tkacik, Gasper and Barton, Nicholas H}, journal = {Genetics}, number = {4}, pages = {1523 -- 1548}, publisher = {Genetics Society of America}, title = {{A general approximation for the dynamics of quantitative traits}}, doi = {10.1534/genetics.115.184127}, volume = {202}, year = {2016}, }