@article{2857, abstract = {In the vibrant field of optogenetics, optics and genetic targeting are combined to commandeer cellular functions, such as the neuronal action potential, by optically stimulating light-sensitive ion channels expressed in the cell membrane. One broadly applicable manifestation of this approach are covalently attached photochromic tethered ligands (PTLs) that allow activating ligand-gated ion channels with outstanding spatial and temporal resolution. Here, we describe all steps towards the successful development and application of PTL-gated ion channels in cell lines and primary cells. The basis for these experiments forms a combination of molecular modeling, genetic engineering, cell culture, and electrophysiology. The light-gated glutamate receptor (LiGluR), which consists of the PTL-functionalized GluK2 receptor, serves as a model.}, author = {Szobota, Stephanie and Mckenzie, Catherine and Janovjak, Harald L}, journal = {Methods in Molecular Biology}, pages = {417 -- 435}, publisher = {Springer}, title = {{Optical control of ligand-gated ion channels}}, doi = {10.1007/978-1-62703-351-0_32}, volume = {998}, year = {2013}, } @article{2858, abstract = {Tumor growth is caused by the acquisition of driver mutations, which enhance the net reproductive rate of cells. Driver mutations may increase cell division, reduce cell death, or allow cells to overcome density-limiting effects. We study the dynamics of tumor growth as one additional driver mutation is acquired. Our models are based on two-type branching processes that terminate in either tumor disappearance or tumor detection. In our first model, both cell types grow exponentially, with a faster rate for cells carrying the additional driver. We find that the additional driver mutation does not affect the survival probability of the lesion, but can substantially reduce the time to reach the detectable size if the lesion is slow growing. In our second model, cells lacking the additional driver cannot exceed a fixed carrying capacity, due to density limitations. In this case, the time to detection depends strongly on this carrying capacity. Our model provides a quantitative framework for studying tumor dynamics during different stages of progression. We observe that early, small lesions need additional drivers, while late stage metastases are only marginally affected by them. These results help to explain why additional driver mutations are typically not detected in fast-growing metastases.}, author = {Reiter, Johannes and Božić, Ivana and Allen, Benjamin and Chatterjee, Krishnendu and Nowak, Martin}, journal = {Evolutionary Applications}, number = {1}, pages = {34 -- 45}, publisher = {Wiley-Blackwell}, title = {{The effect of one additional driver mutation on tumor progression}}, doi = {10.1111/eva.12020}, volume = {6}, year = {2013}, } @article{2859, abstract = {Given a continuous function f:X-R on a topological space, we consider the preimages of intervals and their homology groups and show how to read the ranks of these groups from the extended persistence diagram of f. In addition, we quantify the robustness of the homology classes under perturbations of f using well groups, and we show how to read the ranks of these groups from the same extended persistence diagram. The special case X=R3 has ramifications in the fields of medical imaging and scientific visualization.}, author = {Bendich, Paul and Edelsbrunner, Herbert and Morozov, Dmitriy and Patel, Amit}, journal = {Homology, Homotopy and Applications}, number = {1}, pages = {51 -- 72}, publisher = {International Press}, title = {{Homology and robustness of level and interlevel sets}}, doi = {10.4310/HHA.2013.v15.n1.a3}, volume = {15}, year = {2013}, } @article{2860, abstract = {In the hippocampus, cell assemblies forming mnemonic representations of space are thought to arise as a result of changes in functional connections of pyramidal cells. We have found that CA1 interneuron circuits are also reconfigured during goal-oriented spatial learning through modification of inputs from pyramidal cells. As learning progressed, new pyramidal assemblies expressed in theta cycles alternated with previously established ones, and eventually overtook them. The firing patterns of interneurons developed a relationship to new, learning-related assemblies: some interneurons associated their activity with new pyramidal assemblies while some others dissociated from them. These firing associations were explained by changes in the weight of monosynaptic inputs received by interneurons from new pyramidal assemblies, as these predicted the associational changes. Spatial learning thus engages circuit modifications in the hippocampus that incorporate a redistribution of inhibitory activity that might assist in the segregation of competing pyramidal cell assembly patterns in space and time.}, author = {Dupret, David and O'Neill, Joseph and Csicsvari, Jozsef L}, journal = {Neuron}, number = {1}, pages = {166 -- 180}, publisher = {Elsevier}, title = {{Dynamic reconfiguration of hippocampal interneuron circuits during spatial learning}}, doi = {10.1016/j.neuron.2013.01.033}, volume = {78}, year = {2013}, } @article{2861, abstract = {We consider a two-parameter family of piecewise linear maps in which the moduli of the two slopes take different values. We provide numerical evidence of the existence of some parameter regions in which the Lyapunov exponent and the topological entropy remain constant. Analytical proof of this phenomenon is also given for certain cases. Surprisingly however, the systems with that property are not conjugate as we prove by using kneading theory.}, author = {Botella Soler, Vicente and Oteo, José and Ros, Javier and Glendinning, Paul}, journal = {Journal of Physics A: Mathematical and Theoretical}, number = {12}, publisher = {IOP Publishing Ltd.}, title = {{Lyapunov exponent and topological entropy plateaus in piecewise linear maps}}, doi = {10.1088/1751-8113/46/12/125101}, volume = {46}, year = {2013}, } @article{2862, abstract = {Motile cilia perform crucial functions during embryonic development and throughout adult life. Development of organs containing motile cilia involves regulation of cilia formation (ciliogenesis) and formation of a luminal space (lumenogenesis) in which cilia generate fluid flows. Control of ciliogenesis and lumenogenesis is not yet fully understood, and it remains unclear whether these processes are coupled. In the zebrafish embryo, lethal giant larvae 2 (lgl2) is expressed prominently in ciliated organs. Lgl proteins are involved in establishing cell polarity and have been implicated in vesicle trafficking. Here, we identified a role for Lgl2 in development of ciliated epithelia in Kupffer's vesicle, which directs left-right asymmetry of the embryo; the otic vesicles, which give rise to the inner ear; and the pronephric ducts of the kidney. Using Kupffer's vesicle as a model ciliated organ, we found that depletion of Lgl2 disrupted lumen formation and reduced cilia number and length. Immunofluorescence and time-lapse imaging of Kupffer's vesicle morphogenesis in Lgl2-deficient embryos suggested cell adhesion defects and revealed loss of the adherens junction component E-cadherin at lateral membranes. Genetic interaction experiments indicate that Lgl2 interacts with Rab11a to regulate E-cadherin and mediate lumen formation that is uncoupled from cilia formation. These results uncover new roles and interactions for Lgl2 that are crucial for both lumenogenesis and ciliogenesis and indicate that these processes are genetically separable in zebrafish.}, author = {Tay, Hwee and Schulze, Sabrina and Compagnon, Julien and Foley, Fiona and Heisenberg, Carl-Philipp J and Yost, H Joseph and Abdelilah Seyfried, Salim and Amack, Jeffrey}, journal = {Development}, number = {7}, pages = {1550 -- 1559}, publisher = {Company of Biologists}, title = {{Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle}}, doi = {10.1242/dev.087130}, volume = {140}, year = {2013}, } @article{2863, abstract = {Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. For large populations, direct sampling of these distributions is impossible, and so we must rely on constructing appropriate models. We show here that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. We introduce the stimulus-dependent maximum entropy (SDME) model—a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. We find that the SDME model gives a more accurate account of single cell responses and in particular significantly outperforms uncoupled models in reproducing the distributions of population codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like average surprise and information transmission in a neural population.}, author = {Granot Atedgi, Einat and Tkacik, Gasper and Segev, Ronen and Schneidman, Elad}, journal = {PLoS Computational Biology}, number = {3}, publisher = {Public Library of Science}, title = {{Stimulus-dependent maximum entropy models of neural population codes}}, doi = {10.1371/journal.pcbi.1002922}, volume = {9}, year = {2013}, } @article{2880, abstract = {Lateral root (LR) formation is initiated when pericycle cells accumulate auxin, thereby acquiring founder cell (FC) status and triggering asymmetric cell divisions, giving rise to a new primordium. How this auxin maximum in pericycle cells builds up and remains focused is not understood. We report that the endodermis plays an active role in the regulation of auxin accumulation and is instructive for FCs to progress during the LR initiation (LRI) phase. We describe the functional importance of a PIN3 (PIN-formed) auxin efflux carrier-dependent hormone reflux pathway between overlaying endodermal and pericycle FCs. Disrupting this reflux pathway causes dramatic defects in the progress of FCs towards the next initiation phase. Our data identify an unexpected regulatory function for the endodermis in LRI as part of the fine-tuning mechanism that appears to act as a check point in LR organogenesis after FCs are specified.}, author = {Marhavy, Peter and Vanstraelen, Marleen and De Rybel, Bert and Zhaojun, Ding and Bennett, Malcolm and Beeckman, Tom and Benková, Eva}, journal = {EMBO Journal}, number = {1}, pages = {149 -- 158}, publisher = {Wiley-Blackwell}, title = {{Auxin reflux between the endodermis and pericycle promotes lateral root initiation}}, doi = {10.1038/emboj.2012.303}, volume = {32}, year = {2013}, } @article{2882, abstract = {Gravitropic bending of plant organs is mediated by an asymmetric signaling of the plant hormone auxin between the upper and lower side of the respective organ. Here, we show that also another plant hormone, gibberellic acid (GA), shows asymmetric action during gravitropic responses. Immunodetection using an antibody against GA and monitoring GA signaling output by downstream degradation of DELLA proteins revealed an asymmetric GA distribution and response with the maximum at the lower side of gravistimulated roots. Genetic or pharmacological manipulation of GA levels or response affects gravity-mediated auxin redistribution and root bending response. The higher GA levels at the lower side of the root correlate with increased amounts of PIN-FORMED2 (PIN2) auxin transporter at the plasma membrane. The observed increase in PIN2 stability is caused by a specific GA effect on trafficking of PIN proteins to lytic vacuoles that presumably occurs downstream of brefeldin A-sensitive endosomes. Our results suggest that asymmetric auxin distribution instructive for gravity-induced differential growth is consolidated by the asymmetric action of GA that stabilizes the PIN-dependent auxin stream along the lower side of gravistimulated roots.}, author = {Löfke, Christian and Zwiewka, Marta and Heilmann, Ingo and Van Montagu, Marc and Teichmann, Thomas and Friml, Jirí}, journal = {PNAS}, number = {9}, pages = {3627 -- 3632}, publisher = {National Academy of Sciences}, title = {{Asymmetric gibberellin signaling regulates vacuolar trafficking of PIN auxin transporters during root gravitropism}}, doi = {10.1073/pnas.1300107110}, volume = {110}, year = {2013}, } @article{2883, abstract = {Plant architecture is influenced by the polar, cell-to-cell transport of auxin that is primarily provided and regulated by plasma membrane efflux catalysts of the PIN-FORMED and B family of ABC transporter (ABCB) classes. The latter were shown to require the functionality of the FK506 binding protein42 TWISTED DWARF1 (TWD1), although underlying mechanisms are unclear. By genetic manipulation of TWD1 expression, we show here that TWD1 affects shootward root auxin reflux and, thus, downstream developmental traits, such as epidermal twisting and gravitropism of the root. Using immunological assays, we demonstrate a predominant lateral, mainly outward-facing, plasma membrane location for TWD1 in the root epidermis characterized by the lateral marker ABC transporter G36/PLEIOTROPIC DRUG-RESISTANCE8/PENETRATION3. At these epidermal plasma membrane domains, TWD1 colocalizes with nonpolar ABCB1. In planta bioluminescence resonance energy transfer analysis was used to verify specific ABC transporter B1 (ABCB1)-TWD1 interaction. Our data support a model in which TWD1 promotes lateral ABCB-mediated auxin efflux via protein-protein interaction at the plasma membrane, minimizing reflux from the root apoplast into the cytoplasm.}, author = {Wang, Bangjun and Bailly, Aurélien and Zwiewk, Marta and Henrichs, Sina and Azzarello, Elisa and Mancuso, Stefano and Maeshima, Masayoshi and Friml, Jirí and Schulz, Alexander and Geisler, Markus}, journal = {Plant Cell}, number = {1}, pages = {202 -- 214}, publisher = {American Society of Plant Biologists}, title = {{Arabidopsis TWISTED DWARF1 functionally interacts with auxin exporter ABCB1 on the root plasma membrane}}, doi = {10.1105/tpc.112.105999}, volume = {25}, year = {2013}, } @article{2884, author = {Maître, Jean-Léon and Berthoumieux, Hélène and Krens, Gabriel and Salbreux, Guillaume and Julicher, Frank and Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {Medecine Sciences}, number = {2}, pages = {147 -- 150}, publisher = {Éditions Médicales et Scientifiques}, title = {{Cell adhesion mechanics of zebrafish gastrulation}}, doi = {10.1051/medsci/2013292011}, volume = {29}, year = {2013}, } @proceedings{2885, abstract = {This volume contains the post-proceedings of the 8th Doctoral Workshop on Mathematical and Engineering Methods in Computer Science, MEMICS 2012, held in Znojmo, Czech Republic, in October, 2012. The 13 thoroughly revised papers were carefully selected out of 31 submissions and are presented together with 6 invited papers. The topics covered by the papers include: computer-aided analysis and verification, applications of game theory in computer science, networks and security, modern trends of graph theory in computer science, electronic systems design and testing, and quantum information processing.}, editor = {Kucera, Antonin and Henzinger, Thomas A and Nesetril, Jaroslav and Vojnar, Tomas and Antos, David}, location = {Znojmo, Czech Republic}, pages = {1 -- 228}, publisher = {Springer}, title = {{Mathematical and Engineering Methods in Computer Science}}, doi = {10.1007/978-3-642-36046-6}, volume = {7721}, year = {2013}, } @inproceedings{2886, abstract = {We focus on the realizability problem of Message Sequence Graphs (MSG), i.e. the problem whether a given MSG specification is correctly distributable among parallel components communicating via messages. This fundamental problem of MSG is known to be undecidable. We introduce a well motivated restricted class of MSG, so called controllable-choice MSG, and show that all its models are realizable and moreover it is decidable whether a given MSG model is a member of this class. In more detail, this class of MSG specifications admits a deadlock-free realization by overloading existing messages with additional bounded control data. We also show that the presented class is the largest known subclass of MSG that allows for deadlock-free realization.}, author = {Chmelik, Martin and Řehák, Vojtěch}, location = {Znojmo, Czech Republic}, pages = {118 -- 130}, publisher = {Springer}, title = {{Controllable-choice message sequence graphs}}, doi = {10.1007/978-3-642-36046-6_12}, volume = {7721}, year = {2013}, } @article{2887, abstract = {Root system growth and development is highly plastic and is influenced by the surrounding environment. Roots frequently grow in heterogeneous environments that include interactions from neighboring plants and physical impediments in the rhizosphere. To investigate how planting density and physical objects affect root system growth, we grew rice in a transparent gel system in close proximity with another plant or a physical object. Root systems were imaged and reconstructed in three dimensions. Root-root interaction strength was calculated using quantitative metrics that characterize the extent towhich the reconstructed root systems overlap each other. Surprisingly, we found the overlap of root systems of the same genotype was significantly higher than that of root systems of different genotypes. Root systems of the same genotype tended to grow toward each other but those of different genotypes appeared to avoid each other. Shoot separation experiments excluded the possibility of aerial interactions, suggesting root communication. Staggered plantings indicated that interactions likely occur at root tips in close proximity. Recognition of obstacles also occurred through root tips, but through physical contact in a size-dependent manner. These results indicate that root systems use two different forms of communication to recognize objects and alter root architecture: root-root recognition, possibly mediated through root exudates, and root-object recognition mediated by physical contact at the root tips. This finding suggests that root tips act as local sensors that integrate rhizosphere information into global root architectural changes.}, author = {Fang, Suqin and Clark, Randy and Zheng, Ying and Iyer Pascuzzi, Anjali and Weitz, Joshua and Kochian, Leon and Edelsbrunner, Herbert and Liao, Hong and Benfey, Philip}, journal = {PNAS}, number = {7}, pages = {2670 -- 2675}, publisher = {National Academy of Sciences}, title = {{Genotypic recognition and spatial responses by rice roots}}, doi = {10.1073/pnas.1222821110}, volume = {110}, year = {2013}, } @inproceedings{2901, abstract = { We introduce the M-modes problem for graphical models: predicting the M label configurations of highest probability that are at the same time local maxima of the probability landscape. M-modes have multiple possible applications: because they are intrinsically diverse, they provide a principled alternative to non-maximum suppression techniques for structured prediction, they can act as codebook vectors for quantizing the configuration space, or they can form component centers for mixture model approximation. We present two algorithms for solving the M-modes problem. The first algorithm solves the problem in polynomial time when the underlying graphical model is a simple chain. The second algorithm solves the problem for junction chains. In synthetic and real dataset, we demonstrate how M-modes can improve the performance of prediction. We also use the generated modes as a tool to understand the topography of the probability distribution of configurations, for example with relation to the training set size and amount of noise in the data. }, author = {Chen, Chao and Kolmogorov, Vladimir and Yan, Zhu and Metaxas, Dimitris and Lampert, Christoph}, location = {Scottsdale, AZ, United States}, pages = {161 -- 169}, publisher = {JMLR}, title = {{Computing the M most probable modes of a graphical model}}, volume = {31}, year = {2013}, } @inproceedings{2906, abstract = {Motivated by an application in cell biology, we describe an extension of the kinetic data structures framework from Delaunay triangulations to fixed-radius alpha complexes. Our algorithm is implemented using CGAL, following the exact geometric computation paradigm. We report on several techniques to accelerate the computation that turn our implementation applicable to the underlying biological problem.}, author = {Kerber, Michael and Edelsbrunner, Herbert}, booktitle = {2013 Proceedings of the 15th Workshop on Algorithm Engineering and Experiments}, location = {New Orleans, LA, United States}, pages = {70 -- 77}, publisher = {Society of Industrial and Applied Mathematics}, title = {{3D kinetic alpha complexes and their implementation}}, doi = {10.1137/1.9781611972931.6}, year = {2013}, } @inbook{2907, abstract = {Sex and recombination are among the most striking features of the living world, and they play a crucial role in allowing the evolution of complex adaptation. The sharing of genomes through the sexual union of different individuals requires elaborate behavioral and physiological adaptations. At the molecular level, the alignment of two DNA double helices, followed by their precise cutting and rejoining, is an extraordinary feat. Sex and recombination have diverse—and often surprising—evolutionary consequences: distinct sexes, elaborate mating displays, selfish genetic elements, and so on.}, author = {Barton, Nicholas H}, booktitle = {The Princeton Guide to Evolution}, isbn = {9780691149776}, pages = {328 -- 333}, publisher = {Princeton University Press}, title = {{Recombination and sex}}, year = {2013}, } @article{2908, abstract = {Hybridization is an almost inevitable component of speciation, and its study can tell us much about that process. However, hybridization itself may have a negligible influence on the origin of species: on the one hand, universally favoured alleles spread readily across hybrid zones, whilst on the other, spatially heterogeneous selection causes divergence despite gene flow. Thus, narrow hybrid zones or occasional hybridisation may hardly affect the process of divergence.}, author = {Barton, Nicholas H}, journal = {Journal of Evolutionary Biology}, number = {2}, pages = {267 -- 269}, publisher = {Wiley-Blackwell}, title = {{Does hybridisation influence speciation? }}, doi = {10.1111/jeb.12015}, volume = {26}, year = {2013}, } @article{2909, abstract = {We survey a class of models for spatially structured populations which we have called spatial Λ-Fleming–Viot processes. They arise from a flexible framework for modelling in which the key innovation is that random genetic drift is driven by a Poisson point process of spatial ‘events’. We demonstrate how this overcomes some of the obstructions to modelling populations which evolve in two- (and higher-) dimensional spatial continua, how its predictions match phenomena observed in data and how it fits with classical models. Finally we outline some directions for future research.}, author = {Barton, Nicholas H and Etheridge, Alison and Véber, Amandine}, journal = {Journal of Statistical Mechanics Theory and Experiment}, number = {1}, publisher = {IOP Publishing Ltd.}, title = {{Modelling evolution in a spatial continuum}}, doi = {10.1088/1742-5468/2013/01/P01002}, volume = {2013}, year = {2013}, } @article{2910, abstract = {Coalescent simulation has become an indispensable tool in population genetics and many complex evolutionary scenarios have been incorporated into the basic algorithm. Despite many years of intense interest in spatial structure, however, there are no available methods to simulate the ancestry of a sample of genes that occupy a spatial continuum. This is mainly due to the severe technical problems encountered by the classical model of isolation by distance. A recently introduced model solves these technical problems and provides a solid theoretical basis for the study of populations evolving in continuous space. We present a detailed algorithm to simulate the coalescent process in this model, and provide an efficient implementation of a generalised version of this algorithm as a freely available Python module.}, author = {Kelleher, Jerome and Barton, Nicholas H and Etheridge, Alison}, journal = {Bioinformatics}, number = {7}, pages = {955 -- 956}, publisher = {Oxford University Press}, title = {{Coalescent simulation in continuous space}}, doi = {10.1093/bioinformatics/btt067}, volume = {29}, year = {2013}, }