@article{9477, abstract = {Cytosine methylation is a DNA modification with important regulatory functions in eukaryotes. In flowering plants, sexual reproduction is accompanied by extensive DNA demethylation, which is required for proper gene expression in the endosperm, a nutritive extraembryonic seed tissue. Endosperm arises from a fusion of a sperm cell carried in the pollen and a female central cell. Endosperm DNA demethylation is observed specifically on the chromosomes inherited from the central cell in Arabidopsis thaliana, rice, and maize, and requires the DEMETER DNA demethylase in Arabidopsis. DEMETER is expressed in the central cell before fertilization, suggesting that endosperm demethylation patterns are inherited from the central cell. Down-regulation of the MET1 DNA methyltransferase has also been proposed to contribute to central cell demethylation. However, with the exception of three maize genes, central cell DNA methylation has not been directly measured, leaving the origin and mechanism of endosperm demethylation uncertain. Here, we report genome-wide analysis of DNA methylation in the central cells of Arabidopsis and rice—species that diverged 150 million years ago—as well as in rice egg cells. We find that DNA demethylation in both species is initiated in central cells, which requires DEMETER in Arabidopsis. However, we do not observe a global reduction of CG methylation that would be indicative of lowered MET1 activity; on the contrary, CG methylation efficiency is elevated in female gametes compared with nonsexual tissues. Our results demonstrate that locus-specific, active DNA demethylation in the central cell is the origin of maternal chromosome hypomethylation in the endosperm.}, author = {Park, Kyunghyuk and Kim, M. Yvonne and Vickers, Martin and Park, Jin-Sup and Hyun, Youbong and Okamoto, Takashi and Zilberman, Daniel and Fischer, Robert L. and Feng, Xiaoqi and Choi, Yeonhee and Scholten, Stefan}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {52}, pages = {15138--15143}, publisher = {National Academy of Sciences}, title = {{DNA demethylation is initiated in the central cells of Arabidopsis and rice}}, doi = {10.1073/pnas.1619047114}, volume = {113}, year = {2016}, } @inproceedings{948, abstract = {Experience constantly shapes neural circuits through a variety of plasticity mechanisms. While the functional roles of some plasticity mechanisms are well-understood, it remains unclear how changes in neural excitability contribute to learning. Here, we develop a normative interpretation of intrinsic plasticity (IP) as a key component of unsupervised learning. We introduce a novel generative mixture model that accounts for the class-specific statistics of stimulus intensities, and we derive a neural circuit that learns the input classes and their intensities. We will analytically show that inference and learning for our generative model can be achieved by a neural circuit with intensity-sensitive neurons equipped with a specific form of IP. Numerical experiments verify our analytical derivations and show robust behavior for artificial and natural stimuli. Our results link IP to non-trivial input statistics, in particular the statistics of stimulus intensities for classes to which a neuron is sensitive. More generally, our work paves the way toward new classification algorithms that are robust to intensity variations.}, author = {Monk, Travis and Savin, Cristina and Lücke, Jörg}, location = {Barcelona, Spaine}, pages = {4285 -- 4293}, publisher = {Neural Information Processing Systems}, title = {{Neurons equipped with intrinsic plasticity learn stimulus intensity statistics}}, volume = {29}, year = {2016}, } @misc{9704, abstract = {Emerging infectious diseases (EIDs) have contributed significantly to the current biodiversity crisis, leading to widespread epidemics and population loss. Owing to genetic variation in pathogen virulence, a complete understanding of species decline requires the accurate identification and characterization of EIDs. We explore this issue in the Western honeybee, where increasing mortality of populations in the Northern Hemisphere has caused major concern. Specifically, we investigate the importance of genetic identity of the main suspect in mortality, deformed wing virus (DWV), in driving honeybee loss. Using laboratory experiments and a systematic field survey, we demonstrate that an emerging DWV genotype (DWV-B) is more virulent than the established DWV genotype (DWV-A) and is widespread in the landscape. Furthermore, we show in a simple model that colonies infected with DWV-B collapse sooner than colonies infected with DWV-A. We also identify potential for rapid DWV evolution by revealing extensive genome-wide recombination in vivo. The emergence of DWV-B in naive honeybee populations, including via recombination with DWV-A, could be of significant ecological and economic importance. Our findings emphasize that knowledge of pathogen genetic identity and diversity is critical to understanding drivers of species decline.}, author = {Mcmahon, Dino and Natsopoulou, Myrsini and Doublet, Vincent and Fürst, Matthias and Weging, Silvio and Brown, Mark and Gogol Döring, Andreas and Paxton, Robert}, publisher = {Dryad}, title = {{Data from: Elevated virulence of an emerging viral genotype as a driver of honeybee loss}}, doi = {10.5061/dryad.cq7t1}, year = {2016}, } @misc{9710, abstract = {Much of quantitative genetics is based on the ‘infinitesimal model’, under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest. Stabilising selection can maintain many traits close to their optima, even when the underlying alleles are weakly selected. However, the number of traits that can be optimised is apparently limited to ~4Ne by the ‘drift load’, and this is hard to reconcile with the apparent complexity of many organisms. Just as for the mutation load, this limit can be evaded by a particular form of negative epistasis. A more robust limit is set by the variance in reproductive success. This suggests that selection accumulates information most efficiently in the infinitesimal regime, when selection on individual alleles is weak, and comparable with random drift. A review of evidence on selection strength suggests that although most variance in fitness may be because of alleles with large Nes, substantial amounts of adaptation may be because of alleles in the infinitesimal regime, in which epistasis has modest effects.}, author = {Barton, Nicholas H}, publisher = {Dryad}, title = {{Data from: How does epistasis influence the response to selection?}}, doi = {10.5061/dryad.s5s7r}, year = {2016}, } @misc{9720, abstract = {Summary: Declining populations of bee pollinators are a cause of concern, with major repercussions for biodiversity loss and food security. RNA viruses associated with honeybees represent a potential threat to other insect pollinators, but the extent of this threat is poorly understood. This study aims to attain a detailed understanding of the current and ongoing risk of emerging infectious disease (EID) transmission between managed and wild pollinator species across a wide range of RNA viruses. Within a structured large-scale national survey across 26 independent sites, we quantify the prevalence and pathogen loads of multiple RNA viruses in co-occurring managed honeybee (Apis mellifera) and wild bumblebee (Bombus spp.) populations. We then construct models that compare virus prevalence between wild and managed pollinators. Multiple RNA viruses associated with honeybees are widespread in sympatric wild bumblebee populations. Virus prevalence in honeybees is a significant predictor of virus prevalence in bumblebees, but we remain cautious in speculating over the principle direction of pathogen transmission. We demonstrate species-specific differences in prevalence, indicating significant variation in disease susceptibility or tolerance. Pathogen loads within individual bumblebees may be high and in the case of at least one RNA virus, prevalence is higher in wild bumblebees than in managed honeybee populations. Our findings indicate widespread transmission of RNA viruses between managed and wild bee pollinators, pointing to an interconnected network of potential disease pressures within and among pollinator species. In the context of the biodiversity crisis, our study emphasizes the importance of targeting a wide range of pathogens and defining host associations when considering potential drivers of population decline.}, author = {Mcmahon, Dino and Fürst, Matthias and Caspar, Jesicca and Theodorou, Panagiotis and Brown, Mark and Paxton, Robert}, publisher = {Dryad}, title = {{Data from: A sting in the spit: widespread cross-infection of multiple RNA viruses across wild and managed bees}}, doi = {10.5061/dryad.4b565}, year = {2016}, } @misc{9862, author = {Roux, Camille and Fraisse, Christelle and Romiguier, Jonathan and Anciaux, Youann and Galtier, Nicolas and Bierne, Nicolas}, publisher = {Public Library of Science}, title = {{Simulation study to test the robustness of ABC in face of recent times of divergence}}, doi = {10.1371/journal.pbio.2000234.s016}, year = {2016}, } @misc{9863, author = {Roux, Camille and Fraisse, Christelle and Romiguier, Jonathan and Anciaux, Youann and Galtier, Nicolas and Bierne, Nicolas}, publisher = {Public Library of Science}, title = {{Accessions of surveyed individuals, geographic locations and summary statistics}}, doi = {10.1371/journal.pbio.2000234.s017}, year = {2016}, } @misc{9864, abstract = {Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by, first, reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.}, author = {Fernandes Redondo, Rodrigo A and de Vladar, Harold and Włodarski, Tomasz and Bollback, Jonathan P}, publisher = {The Royal Society}, title = {{Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family}}, doi = {10.6084/m9.figshare.4315652.v1}, year = {2016}, } @misc{9866, author = {Zagórski, Marcin P and Burda, Zdzisław and Wacław, Bartłomiej}, publisher = {Public Library of Science}, title = {{ZIP-archived directory containing all data and computer programs}}, doi = {10.1371/journal.pcbi.1005218.s009}, year = {2016}, } @misc{9867, abstract = {In the beginning of our experiment, subjects were asked to read a few pages on their computer screens that would explain the rules of the subsequent game. Here, we provide these instructions, translated from German.}, author = {Hilbe, Christian and Hagel, Kristin and Milinski, Manfred}, publisher = {Public Library of Science}, title = {{Experimental game instructions}}, doi = {10.1371/journal.pone.0163867.s008}, year = {2016}, } @misc{9868, abstract = {The raw data file containing the experimental decisions of all our study subjects.}, author = {Hilbe, Christian and Hagel, Kristin and Milinski, Manfred}, publisher = {Public Library of Science}, title = {{Experimental data}}, doi = {10.1371/journal.pone.0163867.s009}, year = {2016}, } @misc{9869, abstract = {A lower bound on the error of a positional estimator with limited positional information is derived.}, author = {Hillenbrand, Patrick and Gerland, Ulrich and Tkačik, Gašper}, publisher = {Public Library of Science}, title = {{Error bound on an estimator of position}}, doi = {10.1371/journal.pone.0163628.s001}, year = {2016}, } @misc{9870, abstract = {The effect of noise in the input field on an Ising model is approximated. Furthermore, methods to compute positional information in an Ising model by transfer matrices and Monte Carlo sampling are outlined.}, author = {Hillenbrand, Patrick and Gerland, Ulrich and Tkačik, Gašper}, publisher = {Public Library of Science}, title = {{Computation of positional information in an Ising model}}, doi = {10.1371/journal.pone.0163628.s002}, year = {2016}, } @misc{9871, abstract = {The positional information in a discrete morphogen field with Gaussian noise is computed.}, author = {Hillenbrand, Patrick and Gerland, Ulrich and Tkačik, Gašper}, publisher = {Public Library of Science}, title = {{Computation of positional information in a discrete morphogen field}}, doi = {10.1371/journal.pone.0163628.s003}, year = {2016}, } @misc{9873, author = {Boehm, Alex and Arnoldini, Markus and Bergmiller, Tobias and Röösli, Thomas and Bigosch, Colette and Ackermann, Martin}, publisher = {Public Library of Science}, title = {{Quantification of the growth rate reduction as a consequence of age-specific mortality}}, doi = {10.1371/journal.pgen.1005974.s015}, year = {2016}, } @inproceedings{1082, abstract = {In many applications, it is desirable to extract only the relevant aspects of data. A principled way to do this is the information bottleneck (IB) method, where one seeks a code that maximises information about a relevance variable, Y, while constraining the information encoded about the original data, X. Unfortunately however, the IB method is computationally demanding when data are high-dimensional and/or non-gaussian. Here we propose an approximate variational scheme for maximising a lower bound on the IB objective, analogous to variational EM. Using this method, we derive an IB algorithm to recover features that are both relevant and sparse. Finally, we demonstrate how kernelised versions of the algorithm can be used to address a broad range of problems with non-linear relation between X and Y.}, author = {Chalk, Matthew J and Marre, Olivier and Tkacik, Gasper}, location = {Barcelona, Spain}, pages = {1965--1973}, publisher = {Neural Information Processing Systems}, title = {{Relevant sparse codes with variational information bottleneck}}, volume = {29}, year = {2016}, } @article{1083, abstract = { Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABABreceptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK-INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole-cell recordings revealed slow GABABR-mediated inhibitory postsynaptic currents (IPSCs) in most CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising perisomatic-targeting basket cells (BCs), as well as dendrite-targeting (DT) interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs in CCK-INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR-mediated currents displayed strong desensitization, which was absent in KCTD12-deficient mice. This study highlights that GABABRs differentially control CCK-IN subtypes, and the kinetics and desensitization of GABABR-mediated currents are modulated by KCTD12 proteins. }, author = {Booker, Sam and Althof, Daniel and Gross, Anna and Loreth, Desiree and Müller, Johanna and Unger, Andreas and Fakler, Bernd and Varro, Andrea and Watanabe, Masahiko and Gassmann, Martin and Bettler, Bernhard and Shigemoto, Ryuichi and Vida, Imre and Kulik, Ákos}, journal = {Cerebral Cortex}, number = {3}, pages = {2318 -- 2334}, publisher = {Oxford University Press}, title = {{KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons}}, doi = {10.1093/cercor/bhw090}, volume = {27}, year = {2016}, } @inproceedings{1090, abstract = { While weighted automata provide a natural framework to express quantitative properties, many basic properties like average response time cannot be expressed with weighted automata. Nested weighted automata extend weighted automata and consist of a master automaton and a set of slave automata that are invoked by the master automaton. Nested weighted automata are strictly more expressive than weighted automata (e.g., average response time can be expressed with nested weighted automata), but the basic decision questions have higher complexity (e.g., for deterministic automata, the emptiness question for nested weighted automata is PSPACE-hard, whereas the corresponding complexity for weighted automata is PTIME). We consider a natural subclass of nested weighted automata where at any point at most a bounded number k of slave automata can be active. We focus on automata whose master value function is the limit average. We show that these nested weighted automata with bounded width are strictly more expressive than weighted automata (e.g., average response time with no overlapping requests can be expressed with bound k=1, but not with non-nested weighted automata). We show that the complexity of the basic decision problems (i.e., emptiness and universality) for the subclass with k constant matches the complexity for weighted automata. Moreover, when k is part of the input given in unary we establish PSPACE-completeness.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, location = {Krakow; Poland}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Nested weighted limit-average automata of bounded width}}, doi = {10.4230/LIPIcs.MFCS.2016.24}, volume = {58}, year = {2016}, } @inproceedings{1093, abstract = {We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results. }, author = {Daca, Przemyslaw and Henzinger, Thomas A and Kretinsky, Jan and Petrov, Tatjana}, location = {Quebec City; Canada}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Linear distances between Markov chains}}, doi = {10.4230/LIPIcs.CONCUR.2016.20}, volume = {59}, year = {2016}, } @inbook{1094, abstract = {Immunogold labeling of freeze-fracture replicas has recently been used for high-resolution visualization of protein localization in electron microscopy. This method has higher labeling efficiency than conventional immunogold methods for membrane molecules allowing precise quantitative measurements. However, one of the limitations of freeze-fracture replica immunolabeling is difficulty in keeping structural orientation and identifying labeled profiles in complex tissues like brain. The difficulty is partly due to fragmentation of freeze-fracture replica preparations during labeling procedures and limited morphological clues on the replica surface. To overcome these issues, we introduce here a grid-glued replica method combined with SEM observation. This method allows histological staining before dissolving the tissue and easy handling of replicas during immunogold labeling, and keeps the whole replica surface intact without fragmentation. The procedure described here is also useful for matched double-replica analysis allowing further identification of labeled profiles in corresponding P-face and E-face.}, author = {Harada, Harumi and Shigemoto, Ryuichi}, booktitle = {High-Resolution Imaging of Cellular Proteins}, issn = {1611-3349}, pages = {203 -- 216}, publisher = {Springer}, title = {{Immunogold protein localization on grid-glued freeze-fracture replicas}}, doi = {10.1007/978-1-4939-6352-2_12}, volume = {1474}, year = {2016}, }