TY - JOUR
AB - G protein–coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering of native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized mGluRs (LimGluRs). The light-agonized LimGluR2, on which we focused, was fast, bistable and supported multiple rounds of on/off switching. Light gated two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. We found that the light-antagonized tool LimGluR2-block was able to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalized the optical control to two additional family members: mGluR3 and mGluR6. This system worked in rodent brain slices and in zebrafish in vivo, where we found that mGluR2 modulated the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease.
AU - Levitz, Joshua
AU - Pantoja, Carlos
AU - Gaub, Benjamin
AU - Janovjak, Harald L
AU - Reiner, Andreas
AU - Hoagland, Adam
AU - Schoppik, David
AU - Kane, Brian
AU - Stawski, Philipp
AU - Schier, Alexander
AU - Trauner, Dirk
AU - Isacoff, Ehud
ID - 2856
JF - Nature Neuroscience
TI - Optical control of metabotropic glutamate receptors
VL - 16
ER -
TY - JOUR
AB - 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.
AU - Szobota, Stephanie
AU - Mckenzie, Catherine
AU - Janovjak, Harald L
ID - 2857
JF - Methods in Molecular Biology
TI - Optical control of ligand-gated ion channels
VL - 998
ER -
TY - JOUR
AB - 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.
AU - Reiter, Johannes
AU - Božić, Ivana
AU - Allen, Benjamin
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 2858
IS - 1
JF - Evolutionary Applications
TI - The effect of one additional driver mutation on tumor progression
VL - 6
ER -
TY - JOUR
AB - 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.
AU - Bendich, Paul
AU - Edelsbrunner, Herbert
AU - Morozov, Dmitriy
AU - Patel, Amit
ID - 2859
IS - 1
JF - Homology, Homotopy and Applications
TI - Homology and robustness of level and interlevel sets
VL - 15
ER -
TY - JOUR
AB - 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.
AU - Dupret, David
AU - O'Neill, Joseph
AU - Csicsvari, Jozsef L
ID - 2860
IS - 1
JF - Neuron
TI - Dynamic reconfiguration of hippocampal interneuron circuits during spatial learning
VL - 78
ER -
TY - JOUR
AB - 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.
AU - Botella Soler, Vicente
AU - Oteo, José
AU - Ros, Javier
AU - Glendinning, Paul
ID - 2861
IS - 12
JF - Journal of Physics A: Mathematical and Theoretical
TI - Lyapunov exponent and topological entropy plateaus in piecewise linear maps
VL - 46
ER -
TY - JOUR
AB - 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.
AU - Tay, Hwee
AU - Schulze, Sabrina
AU - Compagnon, Julien
AU - Foley, Fiona
AU - Heisenberg, Carl-Philipp J
AU - Yost, H Joseph
AU - Abdelilah Seyfried, Salim
AU - Amack, Jeffrey
ID - 2862
IS - 7
JF - Development
TI - Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle
VL - 140
ER -
TY - JOUR
AB - 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.
AU - Granot Atedgi, Einat
AU - Tkacik, Gasper
AU - Segev, Ronen
AU - Schneidman, Elad
ID - 2863
IS - 3
JF - PLoS Computational Biology
TI - Stimulus-dependent maximum entropy models of neural population codes
VL - 9
ER -
TY - JOUR
AB - 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.
AU - Marhavy, Peter
AU - Vanstraelen, Marleen
AU - De Rybel, Bert
AU - Zhaojun, Ding
AU - Bennett, Malcolm
AU - Beeckman, Tom
AU - Benková, Eva
ID - 2880
IS - 1
JF - EMBO Journal
TI - Auxin reflux between the endodermis and pericycle promotes lateral root initiation
VL - 32
ER -
TY - JOUR
AB - 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.
AU - Löfke, Christian
AU - Zwiewka, Marta
AU - Heilmann, Ingo
AU - Van Montagu, Marc
AU - Teichmann, Thomas
AU - Friml, Jirí
ID - 2882
IS - 9
JF - PNAS
TI - Asymmetric gibberellin signaling regulates vacuolar trafficking of PIN auxin transporters during root gravitropism
VL - 110
ER -
TY - JOUR
AB - 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.
AU - Wang, Bangjun
AU - Bailly, Aurélien
AU - Zwiewk, Marta
AU - Henrichs, Sina
AU - Azzarello, Elisa
AU - Mancuso, Stefano
AU - Maeshima, Masayoshi
AU - Friml, Jirí
AU - Schulz, Alexander
AU - Geisler, Markus
ID - 2883
IS - 1
JF - Plant Cell
TI - Arabidopsis TWISTED DWARF1 functionally interacts with auxin exporter ABCB1 on the root plasma membrane
VL - 25
ER -
TY - JOUR
AU - Maître, Jean-Léon
AU - Berthoumieux, Hélène
AU - Krens, Gabriel
AU - Salbreux, Guillaume
AU - Julicher, Frank
AU - Paluch, Ewa
AU - Heisenberg, Carl-Philipp J
ID - 2884
IS - 2
JF - Medecine Sciences
TI - Cell adhesion mechanics of zebrafish gastrulation
VL - 29
ER -
TY - GEN
AB - 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.
ED - Kucera, Antonin
ED - Henzinger, Thomas A
ED - Nesetril, Jaroslav
ED - Vojnar, Tomas
ED - Antos, David
ID - 2885
TI - Mathematical and Engineering Methods in Computer Science
VL - 7721
ER -
TY - CONF
AB - 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.
AU - Chmelik, Martin
AU - Řehák, Vojtěch
ID - 2886
TI - Controllable-choice message sequence graphs
VL - 7721
ER -
TY - JOUR
AB - 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.
AU - Fang, Suqin
AU - Clark, Randy
AU - Zheng, Ying
AU - Iyer Pascuzzi, Anjali
AU - Weitz, Joshua
AU - Kochian, Leon
AU - Edelsbrunner, Herbert
AU - Liao, Hong
AU - Benfey, Philip
ID - 2887
IS - 7
JF - PNAS
TI - Genotypic recognition and spatial responses by rice roots
VL - 110
ER -
TY - CONF
AB - 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.
AU - Chen, Chao
AU - Kolmogorov, Vladimir
AU - Yan, Zhu
AU - Metaxas, Dimitris
AU - Lampert, Christoph
ID - 2901
TI - Computing the M most probable modes of a graphical model
VL - 31
ER -
TY - CONF
AB - 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.
AU - Kerber, Michael
AU - Edelsbrunner, Herbert
ID - 2906
T2 - 2013 Proceedings of the 15th Workshop on Algorithm Engineering and Experiments
TI - 3D kinetic alpha complexes and their implementation
ER -
TY - CHAP
AB - 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.
AU - Barton, Nicholas H
ID - 2907
SN - 9780691149776
T2 - The Princeton Guide to Evolution
TI - Recombination and sex
ER -
TY - JOUR
AB - 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.
AU - Barton, Nicholas H
ID - 2908
IS - 2
JF - Journal of Evolutionary Biology
TI - Does hybridisation influence speciation?
VL - 26
ER -
TY - JOUR
AB - 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.
AU - Barton, Nicholas H
AU - Etheridge, Alison
AU - Véber, Amandine
ID - 2909
IS - 1
JF - Journal of Statistical Mechanics Theory and Experiment
TI - Modelling evolution in a spatial continuum
VL - 2013
ER -
TY - JOUR
AB - 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.
AU - Kelleher, Jerome
AU - Barton, Nicholas H
AU - Etheridge, Alison
ID - 2910
IS - 7
JF - Bioinformatics
TI - Coalescent simulation in continuous space
VL - 29
ER -
TY - JOUR
AB - The ability of an organism to distinguish between various stimuli is limited by the structure and noise in the population code of its sensory neurons. Here we infer a distance measure on the stimulus space directly from the recorded activity of 100 neurons in the salamander retina. In contrast to previously used measures of stimulus similarity, this "neural metric" tells us how distinguishable a pair of stimulus clips is to the retina, based on the similarity between the induced distributions of population responses. We show that the retinal distance strongly deviates from Euclidean, or any static metric, yet has a simple structure: we identify the stimulus features that the neural population is jointly sensitive to, and show the support-vector-machine- like kernel function relating the stimulus and neural response spaces. We show that the non-Euclidean nature of the retinal distance has important consequences for neural decoding.
AU - Tkacik, Gasper
AU - Granot Atedgi, Einat
AU - Segev, Ronen
AU - Schneidman, Elad
ID - 2913
IS - 5
JF - Physical Review Letters
TI - Retinal metric: a stimulus distance measure derived from population neural responses
VL - 110
ER -
TY - JOUR
AB - The scale invariance of natural images suggests an analogy to the statistical mechanics of physical systems at a critical point. Here we examine the distribution of pixels in small image patches and show how to construct the corresponding thermodynamics. We find evidence for criticality in a diverging specific heat, which corresponds to large fluctuations in how "surprising" we find individual images, and in the quantitative form of the entropy vs energy. We identify special image configurations as local energy minima and show that average patches within each basin are interpretable as lines and edges in all orientations.
AU - Stephens, Greg
AU - Mora, Thierry
AU - Tkacik, Gasper
AU - Bialek, William
ID - 2914
IS - 1
JF - Physical Review Letters
TI - Statistical thermodynamics of natural images
VL - 110
ER -
TY - JOUR
AB - Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis.
AU - Castanon, Irinka
AU - Abrami, Laurence
AU - Holtzer, Laurent
AU - Heisenberg, Carl-Philipp J
AU - Van Der Goot, Françoise
AU - González Gaitán, Marcos
ID - 2918
IS - 1
JF - Nature Cell Biology
TI - Anthrax toxin receptor 2a controls mitotic spindle positioning
VL - 15
ER -
TY - JOUR
AB - The distribution of the phytohormone auxin regulates many aspects of plant development including growth response to gravity. Gravitropic root curvature involves coordinated and asymmetric cell elongation between the lower and upper side of the root, mediated by differential cellular auxin levels. The asymmetry in the auxin distribution is established and maintained by a spatio-temporal regulation of the PIN-FORMED (PIN) auxin transporter activity. We provide novel insights into the complex regulation of PIN abundance and activity during root gravitropism. We show that PIN2 turnover is differentially regulated on the upper and lower side of gravistimulated roots by distinct but partially overlapping auxin feedback mechanisms. In addition to regulating transcription and clathrin-mediated internalization, auxin also controls PIN abundance at the plasma membrane by promoting their vacuolar targeting and degradation. This effect of elevated auxin levels requires the activity of SKP-Cullin-F-box TIR1/AFB (SCF TIR1/AFB)-dependent pathway. Importantly, also suboptimal auxin levels mediate PIN degradation utilizing the same signalling pathway. These feedback mechanisms are functionally important during gravitropic response and ensure fine-tuning of auxin fluxes for maintaining as well as terminating asymmetric growth.
AU - Baster, Pawel
AU - Robert, Stéphanie
AU - Kleine Vehn, Jürgen
AU - Vanneste, Steffen
AU - Kania, Urszula
AU - Grunewald, Wim
AU - De Rybel, Bert
AU - Beeckman, Tom
AU - Friml, Jirí
ID - 2919
IS - 2
JF - EMBO Journal
TI - SCF^TIR1 AFB-auxin signalling regulates PIN vacuolar trafficking and auxin fluxes during root gravitropism
VL - 32
ER -
TY - JOUR
AB - Cell polarisation in development is a common and fundamental process underlying embryo patterning and morphogenesis, and has been extensively studied over the past years. Our current knowledge of cell polarisation in development is predominantly based on studies that have analysed polarisation of single cells, such as eggs, or cellular aggregates with a stable polarising interface, such as cultured epithelial cells (St Johnston and Ahringer, 2010). However, in embryonic development, particularly of vertebrates, cell polarisation processes often encompass large numbers of cells that are placed within moving and proliferating tissues, and undergo mesenchymal-to-epithelial transitions with a highly complex spatiotemporal choreography. How such intricate cell polarisation processes in embryonic development are achieved has only started to be analysed. By using live imaging of neurulation in the transparent zebrafish embryo, Buckley et al (2012) now describe a novel polarisation strategy by which cells assemble an apical domain in the part of their cell body that intersects with the midline of the forming neural rod. This mechanism, along with the previously described mirror-symmetric divisions (Tawk et al, 2007), is thought to trigger formation of both neural rod midline and lumen.
AU - Compagnon, Julien
AU - Heisenberg, Carl-Philipp J
ID - 2920
IS - 1
JF - EMBO Journal
TI - Neurulation coordinating cell polarisation and lumen formation
VL - 32
ER -
TY - JOUR
AB - In this paper, we present the first output-sensitive algorithm to compute the persistence diagram of a filtered simplicial complex. For any Γ > 0, it returns only those homology classes with persistence at least Γ. Instead of the classical reduction via column operations, our algorithm performs rank computations on submatrices of the boundary matrix. For an arbitrary constant δ ∈ (0, 1), the running time is O (C (1 - δ) Γ R d (n) log n), where C (1 - δ) Γ is the number of homology classes with persistence at least (1 - δ) Γ, n is the total number of simplices in the complex, d its dimension, and R d (n) is the complexity of computing the rank of an n × n matrix with O (d n) nonzero entries. Depending on the choice of the rank algorithm, this yields a deterministic O (C (1 - δ) Γ n 2.376) algorithm, an O (C (1 - δ) Γ n 2.28) Las-Vegas algorithm, or an O (C (1 - δ) Γ n 2 + ε{lunate}) Monte-Carlo algorithm for an arbitrary ε{lunate} > 0. The space complexity of the Monte-Carlo version is bounded by O (d n) = O (n log n).
AU - Chen, Chao
AU - Kerber, Michael
ID - 2939
IS - 4
JF - Computational Geometry: Theory and Applications
TI - An output sensitive algorithm for persistent homology
VL - 46
ER -
TY - CONF
AB - A chain rule for an entropy notion H(.) states that the entropy H(X) of a variable X decreases by at most l if conditioned on an l-bit string A, i.e., H(X|A)>= H(X)-l. More generally, it satisfies a chain rule for conditional entropy if H(X|Y,A)>= H(X|Y)-l.
All natural information theoretic entropy notions we are aware of (like Shannon or min-entropy) satisfy some kind of chain rule for conditional entropy. Moreover, many computational entropy notions (like Yao entropy, unpredictability entropy and several variants of HILL entropy) satisfy the chain rule for conditional entropy, though here not only the quantity decreases by l, but also the quality of the entropy decreases exponentially in l. However, for
the standard notion of conditional HILL entropy (the computational equivalent of min-entropy) the existence of such a rule was unknown so far.
In this paper, we prove that for conditional HILL entropy no meaningful chain rule exists, assuming the existence of one-way permutations: there exist distributions X,Y,A, where A is a distribution over a single bit, but $H(X|Y)>>H(X|Y,A)$, even if we simultaneously allow for a massive degradation in the quality of the entropy.
The idea underlying our construction is based on a surprising connection between the chain rule for HILL entropy and deniable encryption.
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Wadia, Akshay
ED - Sahai, Amit
ID - 2940
TI - A counterexample to the chain rule for conditional HILL entropy, and what deniable encryption has to do with it
VL - 7785
ER -
TY - CONF
AB - Many visual datasets are traditionally used to analyze the performance of different learning techniques. The evaluation is usually done within each dataset, therefore it is questionable if such results are a reliable indicator of true generalization ability. We propose here an algorithm to exploit the existing data resources when learning on a new multiclass problem. Our main idea is to identify an image representation that decomposes orthogonally into two subspaces: a part specific to each dataset, and a part generic to, and therefore shared between, all the considered source sets. This allows us to use the generic representation as un-biased reference knowledge for a novel classification task. By casting the method in the multi-view setting, we also make it possible to use different features for different databases. We call the algorithm MUST, Multitask Unaligned Shared knowledge Transfer. Through extensive experiments on five public datasets, we show that MUST consistently improves the cross-datasets generalization performance.
AU - Tommasi, Tatiana
AU - Quadrianto, Novi
AU - Caputo, Barbara
AU - Lampert, Christoph
ID - 2948
TI - Beyond dataset bias: Multi-task unaligned shared knowledge transfer
VL - 7724
ER -
TY - JOUR
AB - As sessile organisms, plants have to be able to adapt to a continuously changing environment. Plants that perceive some of these changes as stress signals activate signaling pathways to modulate their development and to enable them to survive. The complex responses to environmental cues are to a large extent mediated by plant hormones that together orchestrate the final plant response. The phytohormone cytokinin is involved in many plant developmental processes. Recently, it has been established that cytokinin plays an important role in stress responses, but does not act alone. Indeed, the hormonal control of plant development and stress adaptation is the outcome of a complex network of multiple synergistic and antagonistic interactions between various hormones. Here, we review the recent findings on the cytokinin function as part of this hormonal network. We focus on the importance of the crosstalk between cytokinin and other hormones, such as abscisic acid, jasmonate, salicylic acid, ethylene, and auxin in the modulation of plant development and stress adaptation. Finally, the impact of the current research in the biotechnological industry will be discussed.
AU - O'Brien, José
AU - Benková, Eva
ID - 827
JF - Frontiers in Plant Science
TI - Cytokinin cross talking during biotic and abiotic stress responses
VL - 4
ER -
TY - JOUR
AB - The plant root system is essential for providing anchorage to the soil, supplying minerals and water, and synthesizing metabolites. It is a dynamic organ modulated by external cues such as environmental signals, water and nutrients availability, salinity and others. Lateral roots (LRs) are initiated from the primary root post-embryonically, after which they progress through discrete developmental stages which can be independently controlled, providing a high level of plasticity during root system formation. Within this review, main contributions are presented, from the classical forward genetic screens to the more recent high-throughput approaches, combined with computer model predictions, dissecting how LRs and thereby root system architecture is established and developed.
AU - Cuesta, Candela
AU - Wabnik, Krzysztof T
AU - Benková, Eva
ID - 828
JF - Frontiers in Plant Science
TI - Systems approaches to study root architecture dynamics
VL - 4
ER -
TY - CONF
AB - In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics.
AU - Reiter, Johannes
AU - Božić, Ivana
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 2000
T2 - Proceedings of 25th Int. Conf. on Computer Aided Verification
TI - TTP: Tool for tumor progression
VL - 8044
ER -
TY - JOUR
AB - Traditional statistical methods for confidentiality protection of statistical databases do not scale well to deal with GWAS databases especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach which provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, we propose new methods to release aggregate GWAS data without compromising an individual’s privacy. We present methods for releasing differentially private minor allele frequencies, chi-square statistics and p-values. We compare these approaches on simulated data and on a GWAS study of canine hair length involving 685 dogs. We also propose a privacy-preserving method for finding genome-wide associations based on a differentially-private approach to penalized logistic regression.
AU - Uhler, Caroline
AU - Slavkovic, Aleksandra
AU - Fienberg, Stephen
ID - 2009
IS - 1
JF - Journal of Privacy and Confidentiality
TI - Privacy-preserving data sharing for genome-wide association studies
VL - 5
ER -
TY - JOUR
AB - Many algorithms for inferring causality rely heavily on the faithfulness assumption. The main justification for imposing this assumption is that the set of unfaithful distributions has Lebesgue measure zero, since it can be seen as a collection of hypersurfaces in a hypercube. However, due to sampling error the faithfulness condition alone is not sufficient for statistical estimation, and strong-faithfulness has been proposed and assumed to achieve uniform or high-dimensional consistency. In contrast to the plain faithfulness assumption, the set of distributions that is not strong-faithful has nonzero Lebesgue measure and in fact, can be surprisingly large as we show in this paper. We study the strong-faithfulness condition from a geometric and combinatorial point of view and give upper and lower bounds on the Lebesgue measure of strong-faithful distributions for various classes of directed acyclic graphs. Our results imply fundamental limitations for the PC-algorithm and potentially also for other algorithms based on partial correlation testing in the Gaussian case.
AU - Uhler, Caroline
AU - Raskutti, Garvesh
AU - Bühlmann, Peter
AU - Yu, Bin
ID - 2010
IS - 2
JF - The Annals of Statistics
TI - Geometry of the faithfulness assumption in causal inference
VL - 41
ER -
TY - CONF
AB - There is a trade-off between performance and correctness in implementing concurrent data structures. Better performance may be achieved at the expense of relaxing correctness, by redefining the semantics of data structures. We address such a redefinition of data structure semantics and present a systematic and formal framework for obtaining new data structures by quantitatively relaxing existing ones. We view a data structure as a sequential specification S containing all "legal" sequences over an alphabet of method calls. Relaxing the data structure corresponds to defining a distance from any sequence over the alphabet to the sequential specification: the k-relaxed sequential specification contains all sequences over the alphabet within distance k from the original specification. In contrast to other existing work, our relaxations are semantic (distance in terms of data structure states). As an instantiation of our framework, we present two simple yet generic relaxation schemes, called out-of-order and stuttering relaxation, along with several ways of computing distances. We show that the out-of-order relaxation, when further instantiated to stacks, queues, and priority queues, amounts to tolerating bounded out-of-order behavior, which cannot be captured by a purely syntactic relaxation (distance in terms of sequence manipulation, e.g. edit distance). We give concurrent implementations of relaxed data structures and demonstrate that bounded relaxations provide the means for trading correctness for performance in a controlled way. The relaxations are monotonic which further highlights the trade-off: increasing k increases the number of permitted sequences, which as we demonstrate can lead to better performance. Finally, since a relaxed stack or queue also implements a pool, we actually have new concurrent pool implementations that outperform the state-of-the-art ones.
AU - Henzinger, Thomas A
AU - Kirsch, Christoph
AU - Payer, Hannes
AU - Sezgin, Ali
AU - Sokolova, Ana
ID - 2181
SN - 978-1-4503-1832-7
T2 - Proceedings of the 40th annual ACM SIGPLAN-SIGACT symposium on Principles of programming language
TI - Quantitative relaxation of concurrent data structures
ER -
TY - CONF
AB - We propose a general framework for abstraction with respect to quantitative properties, such as worst-case execution time, or power consumption. Our framework provides a systematic way for counter-example guided abstraction refinement for quantitative properties. The salient aspect of the framework is that it allows anytime verification, that is, verification algorithms that can be stopped at any time (for example, due to exhaustion of memory), and report approximations that improve monotonically when the algorithms are given more time. We instantiate the framework with a number of quantitative abstractions and refinement schemes, which differ in terms of how much quantitative information they keep from the original system. We introduce both state-based and trace-based quantitative abstractions, and we describe conditions that define classes of quantitative properties for which the abstractions provide over-approximations. We give algorithms for evaluating the quantitative properties on the abstract systems. We present algorithms for counter-example based refinements for quantitative properties for both state-based and segment-based abstractions. We perform a case study on worst-case execution time of executables to evaluate the anytime verification aspect and the quantitative abstractions we proposed.
AU - Cerny, Pavol
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 2182
T2 - Proceedings of the 40th annual ACM SIGPLAN-SIGACT symposium on Principles of programming language
TI - Quantitative abstraction refinement
ER -
TY - CONF
AB - A straight skeleton is a well-known geometric structure, and several algorithms exist to construct the straight skeleton for a given polygon or planar straight-line graph. In this paper, we ask the reverse question: Given the straight skeleton (in form of a planar straight-line graph, with some rays to infinity), can we reconstruct a planar straight-line graph for which this was the straight skeleton? We show how to reduce this problem to the problem of finding a line that intersects a set of convex polygons. We can find these convex polygons and all such lines in $O(nlog n)$ time in the Real RAM computer model, where $n$ denotes the number of edges of the input graph. We also explain how our approach can be used for recognizing Voronoi diagrams of points, thereby completing a partial solution provided by Ash and Bolker in 1985.
AU - Biedl, Therese
AU - Held, Martin
AU - Huber, Stefan
ID - 2209
TI - Recognizing straight skeletons and Voronoi diagrams and reconstructing their input
ER -
TY - CONF
AB - A straight skeleton is a well-known geometric structure, and several algorithms exist to construct the straight skeleton for a given polygon. In this paper, we ask the reverse question: Given the straight skeleton (in form of a tree with a drawing in the plane, but with the exact position of the leaves unspecified), can we reconstruct the polygon? We show that in most cases there exists at most one polygon; in the remaining case there is an infinite number of polygons determined by one angle that can range in an interval. We can find this (set of) polygon(s) in linear time in the Real RAM computer model.
AU - Biedl, Therese
AU - Held, Martin
AU - Huber, Stefan
ID - 2210
T2 - 29th European Workshop on Computational Geometry
TI - Reconstructing polygons from embedded straight skeletons
ER -
TY - CONF
AB - We describe new extensions of the Vampire theorem prover for computing tree interpolants. These extensions generalize Craig interpolation in Vampire, and can also be used to derive sequence interpolants. We evaluated our implementation on a large number of examples over the theory of linear integer arithmetic and integer-indexed arrays, with and without quantifiers. When compared to other methods, our experiments show that some examples could only be solved by our implementation.
AU - Blanc, Régis
AU - Gupta, Ashutosh
AU - Kovács, Laura
AU - Kragl, Bernhard
ID - 2237
TI - Tree interpolation in Vampire
VL - 8312
ER -
TY - CONF
AB - We study the problem of achieving a given value in Markov decision processes (MDPs) with several independent discounted reward objectives. We consider a generalised version of discounted reward objectives, in which the amount of discounting depends on the states visited and on the objective. This definition extends the usual definition of discounted reward, and allows to capture the systems in which the value of different commodities diminish at different and variable rates.
We establish results for two prominent subclasses of the problem, namely state-discount models where the discount factors are only dependent on the state of the MDP (and independent of the objective), and reward-discount models where they are only dependent on the objective (but not on the state of the MDP). For the state-discount models we use a straightforward reduction to expected total reward and show that the problem whether a value is achievable can be solved in polynomial time. For the reward-discount model we show that memory and randomisation of the strategies are required, but nevertheless that the problem is decidable and it is sufficient to consider strategies which after a certain number of steps behave in a memoryless way.
For the general case, we show that when restricted to graphs (i.e. MDPs with no randomisation), pure strategies and discount factors of the form 1/n where n is an integer, the problem is in PSPACE and finite memory suffices for achieving a given value. We also show that when the discount factors are not of the form 1/n, the memory required by a strategy can be infinite.
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Wojtczak, Dominik
ID - 2238
TI - Multi-objective discounted reward verification in graphs and MDPs
VL - 8312
ER -
TY - CONF
AB - We show that modal logic over universally first-order definable classes of transitive frames is decidable. More precisely, let K be an arbitrary class of transitive Kripke frames definable by a universal first-order sentence. We show that the global and finite global satisfiability problems of modal logic over K are decidable in NP, regardless of choice of K. We also show that the local satisfiability and the finite local satisfiability problems of modal logic over K are decidable in NEXPTIME.
AU - Michaliszyn, Jakub
AU - Otop, Jan
ID - 2243
TI - Elementary modal logics over transitive structures
VL - 23
ER -
TY - CONF
AB - We consider two systems (α1,...,αm) and (β1,...,βn) of curves drawn on a compact two-dimensional surface ℳ with boundary. Each αi and each βj is either an arc meeting the boundary of ℳ at its two endpoints, or a closed curve. The αi are pairwise disjoint except for possibly sharing endpoints, and similarly for the βj. We want to "untangle" the βj from the αi by a self-homeomorphism of ℳ; more precisely, we seek an homeomorphism φ: ℳ → ℳ fixing the boundary of ℳ pointwise such that the total number of crossings of the αi with the φ(βj) is as small as possible. This problem is motivated by an application in the algorithmic theory of embeddings and 3-manifolds. We prove that if ℳ is planar, i.e., a sphere with h ≥ 0 boundary components ("holes"), then O(mn) crossings can be achieved (independently of h), which is asymptotically tight, as an easy lower bound shows. In general, for an arbitrary (orientable or nonorientable) surface ℳ with h holes and of (orientable or nonorientable) genus g ≥ 0, we obtain an O((m + n)4) upper bound, again independent of h and g.
AU - Matoušek, Jiří
AU - Sedgwick, Eric
AU - Tancer, Martin
AU - Wagner, Uli
ID - 2244
TI - Untangling two systems of noncrossing curves
VL - 8242
ER -
TY - JOUR
AB - Linked (Open) Data - bibliographic data on the Semantic Web. Report of the Working Group on Linked Data to the plenary assembly of the Austrian Library Network (translation of the title). Linked Data stands for a certain approach to publishing data on the Web. The underlying idea is to harmonise heterogeneous data sources of different origin in order to improve their accessibility and interoperability, effectively making them queryable as a big distributed database. This report summarises relevant developments in Europe as well as the Linked Data Working Group‘s strategic and technical considerations regarding the publishing of the Austrian Library Network’s (OBV’s) bibliographic datasets. It concludes with the mutual agreement that the implementation of Linked Data principles within the OBV can only be taken into consideration accompanied by a discussion about the provision of the datasets under a free license.
AU - Danowski, Patrick
AU - Goldfarb, Doron
AU - Schaffner, Verena
AU - Seidler, Wolfram
ID - 2256
IS - 3/4
JF - VÖB Mitteilungen
TI - Linked (Open) Data - Bibliographische Daten im Semantic Web
VL - 66
ER -
TY - CONF
AB - In a digital signature scheme with message recovery, rather than transmitting the message m and its signature σ, a single enhanced signature τ is transmitted. The verifier is able to recover m from τ and at the same time verify its authenticity. The two most important parameters of such a scheme are its security and overhead |τ| − |m|. A simple argument shows that for any scheme with “n bits security” |τ| − |m| ≥ n, i.e., the overhead is lower bounded by the security parameter n. Currently, the best known constructions in the random oracle model are far from this lower bound requiring an overhead of n + logq h , where q h is the number of queries to the random oracle. In this paper we give a construction which basically matches the n bit lower bound. We propose a simple digital signature scheme with n + o(logq h ) bits overhead, where q h denotes the number of random oracle queries.
Our construction works in two steps. First, we propose a signature scheme with message recovery having optimal overhead in a new ideal model, the random invertible function model. Second, we show that a four-round Feistel network with random oracles as round functions is tightly “public-indifferentiable” from a random invertible function. At the core of our indifferentiability proof is an almost tight upper bound for the expected number of edges of the densest “small” subgraph of a random Cayley graph, which may be of independent interest.
AU - Kiltz, Eike
AU - Pietrzak, Krzysztof Z
AU - Szegedy, Mario
ID - 2258
TI - Digital signatures with minimal overhead from indifferentiable random invertible functions
VL - 8042
ER -
TY - CONF
AB - The learning with rounding (LWR) problem, introduced by Banerjee, Peikert and Rosen at EUROCRYPT ’12, is a variant of learning with errors (LWE), where one replaces random errors with deterministic rounding. The LWR problem was shown to be as hard as LWE for a setting of parameters where the modulus and modulus-to-error ratio are super-polynomial. In this work we resolve the main open problem and give a new reduction that works for a larger range of parameters, allowing for a polynomial modulus and modulus-to-error ratio. In particular, a smaller modulus gives us greater efficiency, and a smaller modulus-to-error ratio gives us greater security, which now follows from the worst-case hardness of GapSVP with polynomial (rather than super-polynomial) approximation factors.
As a tool in the reduction, we show that there is a “lossy mode” for the LWR problem, in which LWR samples only reveal partial information about the secret. This property gives us several interesting new applications, including a proof that LWR remains secure with weakly random secrets of sufficient min-entropy, and very simple constructions of deterministic encryption, lossy trapdoor functions and reusable extractors.
Our approach is inspired by a technique of Goldwasser et al. from ICS ’10, which implicitly showed the existence of a “lossy mode” for LWE. By refining this technique, we also improve on the parameters of that work to only requiring a polynomial (instead of super-polynomial) modulus and modulus-to-error ratio.
AU - Alwen, Joel F
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ID - 2259
IS - 1
TI - Learning with rounding, revisited: New reduction properties and applications
VL - 8042
ER -
TY - JOUR
AB - Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia. We used this model to explore the role of synchronization in brain neural networks, a process thought to be dysfunctional in schizophrenia and previously associated with positive, negative, and cognitive symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced an impairment in long-range neural synchrony in adult offspring between two regions implicated in schizophrenia pathology; the hippocampus and the medial prefrontal cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the antipsychotic clozapine. MIA animals have previously been shown to have impaired pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits in animal models. Our data showed that deficits in synchrony were positively correlated with the impairments in PPI. Subsequent analysis of LFP activity during the PPI response also showed that reduced coupling between the mPFC and the hippocampus following processing of the pre-pulse was associated with reduced PPI. The ability of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology provides a useful platform from which to investigate the ontogeny of aberrant synchronous processes. Further, the way in which the model expresses translatable deficits such as aberrant synchrony and reduced PPI will allow researchers to explore novel intervention strategies targeted to these changes.
AU - Dickerson, Desiree
AU - Bilkey, David
ID - 476
IS - DEC
JF - Frontiers in Behavioral Neuroscience
TI - Aberrant neural synchrony in the maternal immune activation model: Using translatable measures to explore targeted interventions
VL - 7
ER -
TY - JOUR
AB - Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.
AU - Wakamoto, Yurichi
AU - Dhar, Neraaj
AU - Chait, Remy P
AU - Schneider, Katrin
AU - Signorino Gelo, François
AU - Leibler, Stanislas
AU - Mckinney, John
ID - 499
IS - 6115
JF - Science
TI - Dynamic persistence of antibiotic-stressed mycobacteria
VL - 339
ER -
TY - JOUR
AB - Background: Reassortment between the RNA segments encoding haemagglutinin (HA) and neuraminidase (NA), the major antigenic influenza proteins, produces viruses with novel HA and NA subtype combinations and has preceded the emergence of pandemic strains. It has been suggested that productive viral infection requires a balance in the level of functional activity of HA and NA, arising from their closely interacting roles in the viral life cycle, and that this functional balance could be mediated by genetic changes in the HA and NA. Here, we investigate how the selective pressure varies for H7 avian influenza HA on different NA subtype backgrounds. Results: By extending Bayesian stochastic mutational mapping methods to calculate the ratio of the rate of non-synonymous change to the rate of synonymous change (d N/d S), we found the average d N/d S across the avian influenza H7 HA1 region to be significantly greater on an N2 NA subtype background than on an N1, N3 or N7 background. Observed differences in evolutionary rates of H7 HA on different NA subtype backgrounds could not be attributed to underlying differences between avian host species or virus pathogenicity. Examination of d N/d S values for each subtype on a site-by-site basis indicated that the elevated d N/d S on the N2 NA background was a result of increased selection, rather than a relaxation of selective constraint. Conclusions: Our results are consistent with the hypothesis that reassortment exposes influenza HA to significant changes in selective pressure through genetic interactions with NA. Such epistatic effects might be explicitly accounted for in future models of influenza evolution.
AU - Ward, Melissa
AU - Lycett, Samantha
AU - Avila, Dorita
AU - Bollback, Jonathan P
AU - Leigh Brown, Andrew
ID - 500
IS - 1
JF - BMC Evolutionary Biology
TI - Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza
VL - 13
ER -
TY - JOUR
AB - All known species of extant tapirs are allopatric: 1 in southeastern Asia and 3 in Central and South America. The fossil record for tapirs, however, is much wider in geographical range, including Europe, Asia, and North and South America, going back to the late Oligocene, making the present distribution a relict of the original one. We here describe a new species of living Tapirus from the Amazon rain forest, the 1st since T. bairdii Gill, 1865, and the 1st new Perissodactyla in more than 100 years, from both morphological and molecular characters. It is shorter in stature than T. terrestris (Linnaeus, 1758) and has distinctive skull morphology, and it is basal to the clade formed by T. terrestris and T. pinchaque (Roulin, 1829). This highlights the unrecognized biodiversity in western Amazonia, where the biota faces increasing threats. Local peoples have long recognized our new species, suggesting a key role for traditional knowledge in understanding the biodiversity of the region.
AU - Cozzuol, Mario
AU - Clozato, Camila
AU - Holanda, Elizete
AU - Rodrigues, Flávio
AU - Nienow, Samuel
AU - De Thoisy, Benoit
AU - Fernandes Redondo, Rodrigo A
AU - Santos, Fabrício
ID - 501
IS - 6
JF - Journal of Mammalogy
TI - A new species of tapir from the Amazon
VL - 94
ER -
TY - JOUR
AB - Blind signatures allow users to obtain signatures on messages hidden from the signer; moreover, the signer cannot link the resulting message/signature pair to the signing session. This paper presents blind signature schemes, in which the number of interactions between the user and the signer is minimal and whose blind signatures are short. Our schemes are defined over bilinear groups and are proved secure in the common-reference-string model without random oracles and under standard assumptions: CDH and the decision-linear assumption. (We also give variants over asymmetric groups based on similar assumptions.) The blind signatures are Waters signatures, which consist of 2 group elements. Moreover, we instantiate partially blind signatures, where the message consists of a part hidden from the signer and a commonly known public part, and schemes achieving perfect blindness. We propose new variants of blind signatures, such as signer-friendly partially blind signatures, where the public part can be chosen by the signer without prior agreement, 3-party blind signatures, as well as blind signatures on multiple aggregated messages provided by independent sources. We also extend Waters signatures to non-binary alphabets by proving a new result on the underlying hash function.
AU - Blazy, Olivier
AU - Fuchsbauer, Georg
AU - Pointcheval, David
AU - Vergnaud, Damien
ID - 502
IS - 5
JF - Journal of Computer Security
TI - Short blind signatures
VL - 21
ER -