@article{10815, abstract = {In the last several decades, developmental biology has clarified the molecular mechanisms of embryogenesis and organogenesis. In particular, it has demonstrated that the “tool-kit genes” essential for regulating developmental processes are not only highly conserved among species, but are also used as systems at various times and places in an organism to control distinct developmental events. Therefore, mutations in many of these tool-kit genes may cause congenital diseases involving morphological abnormalities. This link between genes and abnormal morphological phenotypes underscores the importance of understanding how cells behave and contribute to morphogenesis as a result of gene function. Recent improvements in live imaging and in quantitative analyses of cellular dynamics will advance our understanding of the cellular pathogenesis of congenital diseases associated with aberrant morphologies. In these studies, it is critical to select an appropriate model organism for the particular phenomenon of interest.}, author = {Hashimoto, Masakazu and Morita, Hitoshi and Ueno, Naoto}, issn = {0914-3505}, journal = {Congenital Anomalies}, keywords = {Developmental Biology, Embryology, General Medicine, Pediatrics, Perinatology, and Child Health}, number = {1}, pages = {1--7}, publisher = {Wiley}, title = {{Molecular and cellular mechanisms of development underlying congenital diseases}}, doi = {10.1111/cga.12039}, volume = {54}, year = {2014}, } @article{9458, abstract = {Dnmt1 epigenetically propagates symmetrical CG methylation in many eukaryotes. Their genomes are typically depleted of CG dinucleotides because of imperfect repair of deaminated methylcytosines. Here, we extensively survey diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present and catalyzed by a different DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged more than a billion years ago exhibit clustered methylation, specifically in nucleosome linkers. Clustered methylation occurs at unprecedented densities and directly disfavors nucleosomes, contributing to nucleosome positioning between clusters. Dense methylation is enabled by a regime of genomic sequence evolution that enriches CG dinucleotides and drives the highest CG frequencies known. Species with linker methylation have small, transcriptionally active nuclei that approach the physical limits of chromatin compaction. These features constitute a previously unappreciated genome architecture, in which dense methylation influences nucleosome positions, likely facilitating nuclear processes under extreme spatial constraints.}, author = {Huff, Jason T. and Zilberman, Daniel}, issn = {1097-4172}, journal = {Cell}, number = {6}, pages = {1286--1297}, publisher = {Elsevier}, title = {{Dnmt1-independent CG methylation contributes to nucleosome positioning in diverse eukaryotes}}, doi = {10.1016/j.cell.2014.01.029}, volume = {156}, year = {2014}, } @article{9479, abstract = {Centromeres mediate chromosome segregation and are defined by the centromere-specific histone H3 variant (CenH3)/centromere protein A (CENP-A). Removal of CenH3 from centromeres is a general property of terminally differentiated cells, and the persistence of CenH3 increases the risk of diseases such as cancer. However, active mechanisms of centromere disassembly are unknown. Nondividing Arabidopsis pollen vegetative cells, which transport engulfed sperm by extended tip growth, undergo loss of CenH3; centromeric heterochromatin decondensation; and bulk activation of silent rRNA genes, accompanied by their translocation into the nucleolus. Here, we show that these processes are blocked by mutations in the evolutionarily conserved AAA-ATPase molecular chaperone, CDC48A, homologous to yeast Cdc48 and human p97 proteins, both of which are implicated in ubiquitin/small ubiquitin-like modifier (SUMO)-targeted protein degradation. We demonstrate that CDC48A physically associates with its heterodimeric cofactor UFD1-NPL4, known to bind ubiquitin and SUMO, as well as with SUMO1-modified CenH3 and mutations in NPL4 phenocopy cdc48a mutations. In WT vegetative cell nuclei, genetically unlinked ribosomal DNA (rDNA) loci are uniquely clustered together within the nucleolus and all major rRNA gene variants, including those rDNA variants silenced in leaves, are transcribed. In cdc48a mutant vegetative cell nuclei, however, these rDNA loci frequently colocalized with condensed centromeric heterochromatin at the external periphery of the nucleolus. Our results indicate that the CDC48ANPL4 complex actively removes sumoylated CenH3 from centromeres and disrupts centromeric heterochromatin to release bulk rRNA genes into the nucleolus for ribosome production, which fuels single nucleus-driven pollen tube growth and is essential for plant reproduction.}, author = {Mérai, Zsuzsanna and Chumak, Nina and García-Aguilar, Marcelina and Hsieh, Tzung-Fu and Nishimura, Toshiro and Schoft, Vera K. and Bindics, János and Ślusarz, Lucyna and Arnoux, Stéphanie and Opravil, Susanne and Mechtler, Karl and Zilberman, Daniel and Fischer, Robert L. and Tamaru, Hisashi}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {45}, pages = {16166--16171}, publisher = {National Academy of Sciences}, title = {{The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes}}, doi = {10.1073/pnas.1418564111}, volume = {111}, year = {2014}, } @article{9519, abstract = {Transposons are selfish genetic sequences that can increase their copy number and inflict substantial damage on their hosts. To combat these genomic parasites, plants have evolved multiple pathways to identify and silence transposons by methylating their DNA. Plants have also evolved mechanisms to limit the collateral damage from the antitransposon machinery. In this review, we examine recent developments that have elucidated many of the molecular workings of these pathways. We also highlight the evidence that the methylation and demethylation pathways interact, indicating that plants have a highly sophisticated, integrated system of transposon defense that has an important role in the regulation of gene expression.}, author = {Kim, M. Yvonne and Zilberman, Daniel}, issn = {1878-4372}, journal = {Trends in Plant Science}, number = {5}, pages = {320--326}, publisher = {Elsevier}, title = {{DNA methylation as a system of plant genomic immunity}}, doi = {10.1016/j.tplants.2014.01.014}, volume = {19}, year = {2014}, } @misc{9722, author = {Lovrics, Anna and Gao, Yu and Juhász, Bianka and Bock, István and Byrne, Helen M. and Dinnyés, András and Kovács, Krisztián}, publisher = {Public Library of Science}, title = {{Transition probability between TF expression states when Dbx2 inhibits Nkx2.2}}, doi = {10.1371/journal.pone.0111430.s006}, year = {2014}, } @misc{9739, author = {Chatterjee, Krishnendu and Pavlogiannis, Andreas and Adlam, Ben and Novak, Martin}, publisher = {Public Library of Science}, title = {{Detailed proofs for “The time scale of evolutionary innovation”}}, doi = {10.1371/journal.pcbi.1003818.s001}, year = {2014}, } @misc{9740, abstract = {The fitness effects of symbionts on their hosts can be context-dependent, with usually benign symbionts causing detrimental effects when their hosts are stressed, or typically parasitic symbionts providing protection towards their hosts (e.g. against pathogen infection). Here, we studied the novel association between the invasive garden ant Lasius neglectus and its fungal ectosymbiont Laboulbenia formicarum for potential costs and benefits. We tested ants with different Laboulbenia levels for their survival and immunity under resource limitation and exposure to the obligate killing entomopathogen Metarhizium brunneum. While survival of L. neglectus workers under starvation was significantly decreased with increasing Laboulbenia levels, host survival under Metarhizium exposure increased with higher levels of the ectosymbiont, suggesting a symbiont-mediated anti-pathogen protection, which seems to be driven mechanistically by both improved sanitary behaviours and an upregulated immune system. Ants with high Laboulbenia levels showed significantly longer self-grooming and elevated expression of immune genes relevant for wound repair and antifungal responses (β-1,3-glucan binding protein, Prophenoloxidase), compared with ants carrying low Laboulbenia levels. This suggests that the ectosymbiont Laboulbenia formicarum weakens its ant host by either direct resource exploitation or the costs of an upregulated behavioural and immunological response, which, however, provides a prophylactic protection upon later exposure to pathogens.}, author = {Konrad, Matthias and Grasse, Anna V and Tragust, Simon and Cremer, Sylvia}, publisher = {Dryad}, title = {{Data from: Anti-pathogen protection versus survival costs mediated by an ectosymbiont in an ant host}}, doi = {10.5061/dryad.vm0vc}, year = {2014}, } @misc{9741, abstract = {In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments.}, author = {Lagator, Mato and Colegrave, Nick and Neve, Paul}, publisher = {Dryad}, title = {{Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses}}, doi = {10.5061/dryad.85dn7}, year = {2014}, } @misc{9747, abstract = {Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment.}, author = {Lagator, Mato and Morgan, Andrew and Neve, Paul and Colegrave, Nick}, publisher = {Dryad}, title = {{Data from: Role of sex and migration in adaptation to sink environments}}, doi = {10.5061/dryad.s42n1}, year = {2014}, } @misc{9752, abstract = {Redundancies and correlations in the responses of sensory neurons may seem to waste neural resources, but they can also carry cues about structured stimuli and may help the brain to correct for response errors. To investigate the effect of stimulus structure on redundancy in retina, we measured simultaneous responses from populations of retinal ganglion cells presented with natural and artificial stimuli that varied greatly in correlation structure; these stimuli and recordings are publicly available online. Responding to spatio-temporally structured stimuli such as natural movies, pairs of ganglion cells were modestly more correlated than in response to white noise checkerboards, but they were much less correlated than predicted by a non-adapting functional model of retinal response. Meanwhile, responding to stimuli with purely spatial correlations, pairs of ganglion cells showed increased correlations consistent with a static, non-adapting receptive field and nonlinearity. We found that in response to spatio-temporally correlated stimuli, ganglion cells had faster temporal kernels and tended to have stronger surrounds. These properties of individual cells, along with gain changes that opposed changes in effective contrast at the ganglion cell input, largely explained the pattern of pairwise correlations across stimuli where receptive field measurements were possible.}, author = {Simmons, Kristina and Prentice, Jason and Tkačik, Gašper and Homann, Jan and Yee, Heather and Palmer, Stephanie and Nelson, Philip and Balasubramanian, Vijay}, publisher = {Dryad}, title = {{Data from: Transformation of stimulus correlations by the retina}}, doi = {10.5061/dryad.246qg}, year = {2014}, } @misc{9753, abstract = {Background: The brood of ants and other social insects is highly susceptible to pathogens, particularly those that penetrate the soft larval and pupal cuticle. We here test whether the presence of a pupal cocoon, which occurs in some ant species but not in others, affects the sanitary brood care and fungal infection patterns after exposure to the entomopathogenic fungus Metarhizium brunneum. We use a) a comparative approach analysing four species with either naked or cocooned pupae and b) a within-species analysis of a single ant species, in which both pupal types co-exist in the same colony. Results: We found that the presence of a cocoon did not compromise fungal pathogen detection by the ants and that species with cocooned pupae increased brood grooming after pathogen exposure. All tested ant species further removed brood from their nests, which was predominantly expressed towards larvae and naked pupae treated with the live fungal pathogen. In contrast, cocooned pupae exposed to live fungus were not removed at higher rates than cocooned pupae exposed to dead fungus or a sham control. Consistent with this, exposure to the live fungus caused high numbers of infections and fungal outgrowth in larvae and naked pupae, but not in cocooned pupae. Moreover, the ants consistently removed the brood prior to fungal outgrowth, ensuring a clean brood chamber. Conclusion: Our study suggests that the pupal cocoon has a protective effect against fungal infection, causing an adaptive change in sanitary behaviours by the ants. It further demonstrates that brood removal - originally described for honeybees as “hygienic behaviour” – is a widespread sanitary behaviour in ants, which likely has important implications on disease dynamics in social insect colonies.}, author = {Tragust, Simon and Ugelvig, Line V and Chapuisat, Michel and Heinze, Jürgen and Cremer, Sylvia}, publisher = {Dryad}, title = {{Data from: Pupal cocoons affect sanitary brood care and limit fungal infections in ant colonies}}, doi = {10.5061/dryad.nc0gc}, year = {2014}, } @misc{9888, abstract = {Detailed description of the experimental prodedures, data analyses and additional statistical analyses of the results.}, author = {Wolf, Stephan and Mcmahon, Dino and Lim, Ka and Pull, Christopher and Clark, Suzanne and Paxton, Robert and Osborne, Juliet}, publisher = {Public Library of Science}, title = {{Supporting information}}, doi = {10.1371/journal.pone.0103989.s003}, year = {2014}, } @article{9931, abstract = {Gene duplication is important in evolution, because it provides new raw material for evolutionary adaptations. Several existing hypotheses about the causes of duplicate retention and diversification differ in their emphasis on gene dosage, subfunctionalization, and neofunctionalization. Little experimental data exist on the relative importance of gene expression changes and changes in coding regions for the evolution of duplicate genes. Furthermore, we do not know how strongly the environment could affect this importance. To address these questions, we performed evolution experiments with the TEM-1 beta lactamase gene in Escherichia coli to study the initial stages of duplicate gene evolution in the laboratory. We mimicked tandem duplication by inserting two copies of the TEM-1 gene on the same plasmid. We then subjected these copies to repeated cycles of mutagenesis and selection in various environments that contained antibiotics in different combinations and concentrations. Our experiments showed that gene dosage is the most important factor in the initial stages of duplicate gene evolution, and overshadows the importance of point mutations in the coding region.}, author = {Dhar, Riddhiman and Bergmiller, Tobias and Wagner, Andreas}, issn = {1558-5646}, journal = {Evolution}, number = {6}, pages = {1775--1791}, publisher = {Wiley}, title = {{Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes}}, doi = {10.1111/evo.12373}, volume = {68}, year = {2014}, } @misc{9932, abstract = {Gene duplication is important in evolution, because it provides new raw material for evolutionary adaptations. Several existing hypotheses about the causes of duplicate retention and diversification differ in their emphasis on gene dosage, sub-functionalization, and neo-functionalization. Little experimental data exists on the relative importance of gene expression changes and changes in coding regions for the evolution of duplicate genes. Furthermore, we do not know how strongly the environment could affect this importance. To address these questions, we performed evolution experiments with the TEM-1 beta lactamase gene in E. coli to study the initial stages of duplicate gene evolution in the laboratory. We mimicked tandem duplication by inserting two copies of the TEM-1 gene on the same plasmid. We then subjected these copies to repeated cycles of mutagenesis and selection in various environments that contained antibiotics in different combinations and concentrations. Our experiments showed that gene dosage is the most important factor in the initial stages of duplicate gene evolution, and overshadows the importance of point mutations in the coding region.}, author = {Dhar, Riddhiman and Bergmiller, Tobias and Wagner, Andreas}, publisher = {Dryad}, title = {{Data from: Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes}}, doi = {10.5061/dryad.jc402}, year = {2014}, } @inbook{10817, abstract = {The Morse-Smale complex can be either explicitly or implicitly represented. Depending on the type of representation, the simplification of the Morse-Smale complex works differently. In the explicit representation, the Morse-Smale complex is directly simplified by explicitly reconnecting the critical points during the simplification. In the implicit representation, on the other hand, the Morse-Smale complex is given by a combinatorial gradient field. In this setting, the simplification changes the combinatorial flow, which yields an indirect simplification of the Morse-Smale complex. The topological complexity of the Morse-Smale complex is reduced in both representations. However, the simplifications generally yield different results. In this chapter, we emphasize properties of the two representations that cause these differences. We also provide a complexity analysis of the two schemes with respect to running time and memory consumption.}, author = {Günther, David and Reininghaus, Jan and Seidel, Hans-Peter and Weinkauf, Tino}, booktitle = {Topological Methods in Data Analysis and Visualization III.}, editor = {Bremer, Peer-Timo and Hotz, Ingrid and Pascucci, Valerio and Peikert, Ronald}, isbn = {9783319040981}, issn = {2197-666X}, pages = {135--150}, publisher = {Springer Nature}, title = {{Notes on the simplification of the Morse-Smale complex}}, doi = {10.1007/978-3-319-04099-8_9}, year = {2014}, } @inproceedings{10884, abstract = {We revisit the parameterized model checking problem for token-passing systems and specifications in indexed CTL  ∗ \X. Emerson and Namjoshi (1995, 2003) have shown that parameterized model checking of indexed CTL  ∗ \X in uni-directional token rings can be reduced to checking rings up to some cutoff size. Clarke et al. (2004) have shown a similar result for general topologies and indexed LTL \X, provided processes cannot choose the directions for sending or receiving the token. We unify and substantially extend these results by systematically exploring fragments of indexed CTL  ∗ \X with respect to general topologies. For each fragment we establish whether a cutoff exists, and for some concrete topologies, such as rings, cliques and stars, we infer small cutoffs. Finally, we show that the problem becomes undecidable, and thus no cutoffs exist, if processes are allowed to choose the directions in which they send or from which they receive the token.}, author = {Aminof, Benjamin and Jacobs, Swen and Khalimov, Ayrat and Rubin, Sasha}, booktitle = {Verification, Model Checking, and Abstract Interpretation}, isbn = {9783642540127}, issn = {1611-3349}, location = {San Diego, CA, United States}, pages = {262--281}, publisher = {Springer Nature}, title = {{Parameterized model checking of token-passing systems}}, doi = {10.1007/978-3-642-54013-4_15}, volume = {8318}, year = {2014}, } @inproceedings{10885, abstract = {Two-player games on graphs provide the theoretical framework for many important problems such as reactive synthesis. While the traditional study of two-player zero-sum games has been extended to multi-player games with several notions of equilibria, they are decidable only for perfect-information games, whereas several applications require imperfect-information games. In this paper we propose a new notion of equilibria, called doomsday equilibria, which is a strategy profile such that all players satisfy their own objective, and if any coalition of players deviates and violates even one of the players objective, then the objective of every player is violated. We present algorithms and complexity results for deciding the existence of doomsday equilibria for various classes of ω-regular objectives, both for imperfect-information games, and for perfect-information games.We provide optimal complexity bounds for imperfect-information games, and in most cases for perfect-information games.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Filiot, Emmanuel and Raskin, Jean-François}, booktitle = {VMCAI 2014: Verification, Model Checking, and Abstract Interpretation}, isbn = {9783642540127}, issn = {1611-3349}, location = {San Diego, CA, United States}, pages = {78--97}, publisher = {Springer Nature}, title = {{Doomsday equilibria for omega-regular games}}, doi = {10.1007/978-3-642-54013-4_5}, volume = {8318}, year = {2014}, } @inproceedings{10886, abstract = {We propose a method for visualizing two-dimensional symmetric positive definite tensor fields using the Heat Kernel Signature (HKS). The HKS is derived from the heat kernel and was originally introduced as an isometry invariant shape signature. Each positive definite tensor field defines a Riemannian manifold by considering the tensor field as a Riemannian metric. On this Riemmanian manifold we can apply the definition of the HKS. The resulting scalar quantity is used for the visualization of tensor fields. The HKS is closely related to the Gaussian curvature of the Riemannian manifold and the time parameter of the heat kernel allows a multiscale analysis in a natural way. In this way, the HKS represents field related scale space properties, enabling a level of detail analysis of tensor fields. This makes the HKS an interesting new scalar quantity for tensor fields, which differs significantly from usual tensor invariants like the trace or the determinant. A method for visualization and a numerical realization of the HKS for tensor fields is proposed in this chapter. To validate the approach we apply it to some illustrating simple examples as isolated critical points and to a medical diffusion tensor data set.}, author = {Zobel, Valentin and Reininghaus, Jan and Hotz, Ingrid}, booktitle = {Topological Methods in Data Analysis and Visualization III }, isbn = {9783319040981}, issn = {2197-666X}, pages = {249--262}, publisher = {Springer}, title = {{Visualization of two-dimensional symmetric positive definite tensor fields using the heat kernel signature}}, doi = {10.1007/978-3-319-04099-8_16}, year = {2014}, } @inproceedings{10892, abstract = {In this paper, we introduce planar matchings on directed pseudo-line arrangements, which yield a planar set of pseudo-line segments such that only matching-partners are adjacent. By translating the planar matching problem into a corresponding stable roommates problem we show that such matchings always exist. Using our new framework, we establish, for the first time, a complete, rigorous definition of weighted straight skeletons, which are based on a so-called wavefront propagation process. We present a generalized and unified approach to treat structural changes in the wavefront that focuses on the restoration of weak planarity by finding planar matchings.}, author = {Biedl, Therese and Huber, Stefan and Palfrader, Peter}, booktitle = {25th International Symposium, ISAAC 2014}, isbn = {9783319130743}, issn = {1611-3349}, location = {Jeonju, Korea}, pages = {117--127}, publisher = {Springer Nature}, title = {{Planar matchings for weighted straight skeletons}}, doi = {10.1007/978-3-319-13075-0_10}, volume = {8889}, year = {2014}, } @inbook{10893, abstract = {Saddle periodic orbits are an essential and stable part of the topological skeleton of a 3D vector field. Nevertheless, there is currently no efficient algorithm to robustly extract these features. In this chapter, we present a novel technique to extract saddle periodic orbits. Exploiting the analytic properties of such an orbit, we propose a scalar measure based on the finite-time Lyapunov exponent (FTLE) that indicates its presence. Using persistent homology, we can then extract the robust cycles of this field. These cycles thereby represent the saddle periodic orbits of the given vector field. We discuss the different existing FTLE approximation schemes regarding their applicability to this specific problem and propose an adapted version of FTLE called Normalized Velocity Separation. Finally, we evaluate our method using simple analytic vector field data.}, author = {Kasten, Jens and Reininghaus, Jan and Reich, Wieland and Scheuermann, Gerik}, booktitle = {Topological Methods in Data Analysis and Visualization III }, editor = {Bremer, Peer-Timo and Hotz, Ingrid and Pascucci, Valerio and Peikert, Ronald}, isbn = {9783319040981}, issn = {2197-666X}, pages = {55--69}, publisher = {Springer}, title = {{Toward the extraction of saddle periodic orbits}}, doi = {10.1007/978-3-319-04099-8_4}, volume = {1}, year = {2014}, }