@article{1538,
  abstract     = {Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time.},
  author       = {Ruess, Jakob and Parise, Francesca and Milias Argeitis, Andreas and Khammash, Mustafa and Lygeros, John},
  journal      = {PNAS},
  number       = {26},
  pages        = {8148 -- 8153},
  publisher    = {National Academy of Sciences},
  title        = {{Iterative experiment design guides the characterization of a light-inducible gene expression circuit}},
  doi          = {10.1073/pnas.1423947112},
  volume       = {112},
  year         = {2015},
}

@article{1539,
  abstract     = {Many stochastic models of biochemical reaction networks contain some chemical species for which the number of molecules that are present in the system can only be finite (for instance due to conservation laws), but also other species that can be present in arbitrarily large amounts. The prime example of such networks are models of gene expression, which typically contain a small and finite number of possible states for the promoter but an infinite number of possible states for the amount of mRNA and protein. One of the main approaches to analyze such models is through the use of equations for the time evolution of moments of the chemical species. Recently, a new approach based on conditional moments of the species with infinite state space given all the different possible states of the finite species has been proposed. It was argued that this approach allows one to capture more details about the full underlying probability distribution with a smaller number of equations. Here, I show that the result that less moments provide more information can only stem from an unnecessarily complicated description of the system in the classical formulation. The foundation of this argument will be the derivation of moment equations that describe the complete probability distribution over the finite state space but only low-order moments over the infinite state space. I will show that the number of equations that is needed is always less than what was previously claimed and always less than the number of conditional moment equations up to the same order. To support these arguments, a symbolic algorithm is provided that can be used to derive minimal systems of unconditional moment equations for models with partially finite state space. },
  author       = {Ruess, Jakob},
  journal      = {Journal of Chemical Physics},
  number       = {24},
  publisher    = {American Institute of Physics},
  title        = {{Minimal moment equations for stochastic models of biochemical reaction networks with partially finite state space}},
  doi          = {10.1063/1.4937937},
  volume       = {143},
  year         = {2015},
}

@article{1540,
  abstract     = {Plant sexual reproduction involves highly structured and specialized organs: stamens (male) and gynoecia (female, containing ovules). These organs synchronously develop within protective flower buds, until anthesis, via tightly coordinated mechanisms that are essential for effective fertilization and production of viable seeds. The phytohormone auxin is one of the key endogenous signalling molecules controlling initiation and development of these, and other, plant organs. In particular, its uneven distribution, resulting from tightly controlled production, metabolism and directional transport, is an important morphogenic factor. In this review we discuss how developmentally controlled and localized auxin biosynthesis and transport contribute to the coordinated development of plants' reproductive organs, and their fertilized derivatives (embryos) via the regulation of auxin levels and distribution within and around them. Current understanding of the links between de novo local auxin biosynthesis, auxin transport and/or signalling is presented to highlight the importance of the non-cell autonomous action of auxin production on development and morphogenesis of reproductive organs and embryos. An overview of transcription factor families, which spatiotemporally define local auxin production by controlling key auxin biosynthetic enzymes, is also presented.},
  author       = {Robert, Hélène and Crhák Khaitová, Lucie and Mroue, Souad and Benková, Eva},
  journal      = {Journal of Experimental Botany},
  number       = {16},
  pages        = {5029 -- 5042},
  publisher    = {Oxford University Press},
  title        = {{The importance of localized auxin production for morphogenesis of reproductive organs and embryos in Arabidopsis}},
  doi          = {10.1093/jxb/erv256},
  volume       = {66},
  year         = {2015},
}

@inproceedings{1541,
  abstract     = {We present XSpeed a parallel state-space exploration algorithm for continuous systems with linear dynamics and nondeterministic inputs. The motivation of having parallel algorithms is to exploit the computational power of multi-core processors to speed-up performance. The parallelization is achieved on two fronts. First, we propose a parallel implementation of the support function algorithm by sampling functions in parallel. Second, we propose a parallel state-space exploration by slicing the time horizon and computing the reachable states in the time slices in parallel. The second method can be however applied only to a class of linear systems with invertible dynamics and fixed input. A GP-GPU implementation is also presented following a lazy evaluation strategy on support functions. The parallel algorithms are implemented in the tool XSpeed. We evaluated the performance on two benchmarks including an 28 dimension Helicopter model. Comparison with the sequential counterpart shows a maximum speed-up of almost 7× on a 6 core, 12 thread Intel Xeon CPU E5-2420 processor. Our GP-GPU implementation shows a maximum speed-up of 12× over the sequential implementation and 53× over SpaceEx (LGG scenario), the state of the art tool for reachability analysis of linear hybrid systems. Experiments illustrate that our parallel algorithm with time slicing not only speeds-up performance but also improves precision.},
  author       = {Ray, Rajarshi and Gurung, Amit and Das, Binayak and Bartocci, Ezio and Bogomolov, Sergiy and Grosu, Radu},
  location     = {Haifa, Israel},
  pages        = {3 -- 18},
  publisher    = {Springer},
  title        = {{XSpeed: Accelerating reachability analysis on multi-core processors}},
  doi          = {10.1007/978-3-319-26287-1_1},
  volume       = {9434},
  year         = {2015},
}

@article{1542,
  abstract     = {The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. },
  author       = {Paixao, Tiago and Badkobeh, Golnaz and Barton, Nicholas H and Çörüş, Doğan and Dang, Duccuong and Friedrich, Tobias and Lehre, Per and Sudholt, Dirk and Sutton, Andrew and Trubenova, Barbora},
  journal      = { Journal of Theoretical Biology},
  pages        = {28 -- 43},
  publisher    = {Elsevier},
  title        = {{Toward a unifying framework for evolutionary processes}},
  doi          = {10.1016/j.jtbi.2015.07.011},
  volume       = {383},
  year         = {2015},
}

@article{1543,
  abstract     = {A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta.},
  author       = {Olvera Carrillo, Yadira and Van Bel, Michiel and Van Hautegem, Tom and Fendrych, Matyas and Huysmans, Marlies and Šimášková, Mária and Van Durme, Matthias and Buscaill, Pierre and Rivas, Susana and Coll, Núria and Coppens, Frederik and Maere, Steven and Nowack, Moritz},
  journal      = {Plant Physiology},
  number       = {4},
  pages        = {2684 -- 2699},
  publisher    = {American Society of Plant Biologists},
  title        = {{A conserved core of programmed cell death indicator genes discriminates developmentally and environmentally induced programmed cell death in plants}},
  doi          = {10.1104/pp.15.00769},
  volume       = {169},
  year         = {2015},
}

@inbook{1544,
  abstract     = {Cell division in prokaryotes and eukaryotes is commonly initiated by the well-controlled binding of proteins to the cytoplasmic side of the cell membrane. However, a precise characterization of the spatiotemporal dynamics of membrane-bound proteins is often difficult to achieve in vivo. Here, we present protocols for the use of supported lipid bilayers to rebuild the cytokinetic machineries of cells with greatly different dimensions: the bacterium Escherichia coli and eggs of the vertebrate Xenopus laevis. Combined with total internal reflection fluorescence microscopy, these experimental setups allow for precise quantitative analyses of membrane-bound proteins. The protocols described to obtain glass-supported membranes from bacterial and vertebrate lipids can be used as starting points for other reconstitution experiments. We believe that similar biochemical assays will be instrumental to study the biochemistry and biophysics underlying a variety of complex cellular tasks, such as signaling, vesicle trafficking, and cell motility.},
  author       = {Nguyen, Phuong and Field, Christine and Groen, Aaron and Mitchison, Timothy and Loose, Martin},
  booktitle    = {Building a Cell from its Components Parts},
  pages        = {223 -- 241},
  publisher    = {Academic Press},
  title        = {{Using supported bilayers to study the spatiotemporal organization of membrane-bound proteins}},
  doi          = {10.1016/bs.mcb.2015.01.007},
  volume       = {128},
  year         = {2015},
}

@article{1546,
  abstract     = {Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (&lt;30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This &quot;perimeter release model&quot; provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.},
  author       = {Nakamura, Yukihiro and Harada, Harumi and Kamasawa, Naomi and Matsui, Ko and Rothman, Jason and Shigemoto, Ryuichi and Silver, R Angus and Digregorio, David and Takahashi, Tomoyuki},
  journal      = {Neuron},
  number       = {1},
  pages        = {145 -- 158},
  publisher    = {Elsevier},
  title        = {{Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development}},
  doi          = {10.1016/j.neuron.2014.11.019},
  volume       = {85},
  year         = {2015},
}

@article{1547,
  abstract     = {Let G be a graph on the vertex set V(G) = {x1,…,xn} with the edge set E(G), and let R = K[x1,…, xn] be the polynomial ring over a field K. Two monomial ideals are associated to G, the edge ideal I(G) generated by all monomials xixj with {xi,xj} ∈ E(G), and the vertex cover ideal IG generated by monomials ∏xi∈Cxi for all minimal vertex covers C of G. A minimal vertex cover of G is a subset C ⊂ V(G) such that each edge has at least one vertex in C and no proper subset of C has the same property. Indeed, the vertex cover ideal of G is the Alexander dual of the edge ideal of G. In this paper, for an unmixed bipartite graph G we consider the lattice of vertex covers LG and we explicitly describe the minimal free resolution of the ideal associated to LG which is exactly the vertex cover ideal of G. Then we compute depth, projective dimension, regularity and extremal Betti numbers of R/I(G) in terms of the associated lattice.},
  author       = {Mohammadi, Fatemeh and Moradi, Somayeh},
  issn         = {2234-3016},
  journal      = {Bulletin of the Korean Mathematical Society},
  number       = {3},
  pages        = {977 -- 986},
  publisher    = {Korean Mathematical Society},
  title        = {{Resolution of unmixed bipartite graphs}},
  doi          = {10.4134/BKMS.2015.52.3.977},
  volume       = {52},
  year         = {2015},
}

@article{1548,
  abstract     = {Reproduction within a host and transmission to the next host are crucial for the virulence and fitness of pathogens. Nevertheless, basic knowledge about such parameters is often missing from the literature, even for well-studied bacteria, such as Bacillus thuringiensis, an endospore-forming insect pathogen, which infects its hosts via the oral route. To characterize bacterial replication success, we made use of an experimental oral infection system for the red flour beetle Tribolium castaneum and developed a flow cytometric assay for the quantification of both spore ingestion by the individual beetle larvae and the resulting spore load after bacterial replication and resporulation within cadavers. On average, spore numbers increased 460-fold, showing that Bacillus thuringiensis grows and replicates successfully in insect cadavers. By inoculating cadaver-derived spores and spores from bacterial stock cultures into nutrient medium, we next investigated outgrowth characteristics of vegetative cells and found that cadaver- derived bacteria showed reduced growth compared to bacteria from the stock cultures. Interestingly, this reduced growth was a consequence of inhibited spore germination, probably originating from the host and resulting in reduced host mortality in subsequent infections by cadaver-derived spores. Nevertheless, we further showed that Bacillus thuringiensis transmission was possible via larval cannibalism when no other food was offered. These results contribute to our understanding of the ecology of Bacillus thuringiensis as an insect pathogen.},
  author       = {Milutinovic, Barbara and Höfling, Christina and Futo, Momir and Scharsack, Jörn and Kurtz, Joachim},
  journal      = {Applied and Environmental Microbiology},
  number       = {23},
  pages        = {8135 -- 8144},
  publisher    = {American Society for Microbiology},
  title        = {{Infection of Tribolium castaneum with Bacillus thuringiensis: Quantification of bacterial replication within cadavers, transmission via cannibalism, and inhibition of spore germination}},
  doi          = {10.1128/AEM.02051-15},
  volume       = {81},
  year         = {2015},
}

@inbook{1549,
  abstract     = {Nature has incorporated small photochromic molecules, colloquially termed 'photoswitches', in photoreceptor proteins to sense optical cues in photo-taxis and vision. While Nature's ability to employ light-responsive functionalities has long been recognized, it was not until recently that scientists designed, synthesized and applied synthetic photochromes to manipulate many of which open rapidly and locally in their native cell types, biological processes with the temporal and spatial resolution of light. Ion channels in particular have come to the forefront of proteins that can be put under the designer control of synthetic photochromes. Photochromic ion channel controllers are comprised of three classes, photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and photochromic crosslinkers (PXs), and in each class ion channel functionality is controlled through reversible changes in photochrome structure. By acting as light-dependent ion channel agonists, antagonist or modulators, photochromic controllers effectively converted a wide range of ion channels, including voltage-gated ion channels, 'leak channels', tri-, tetra- and pentameric ligand-gated ion channels, and temperaturesensitive ion channels, into man-made photoreceptors. Control by photochromes can be reversible, unlike in the case of 'caged' compounds, and non-invasive with high spatial precision, unlike pharmacology and electrical manipulation. Here, we introduce design principles of emerging photochromic molecules that act on ion channels and discuss the impact that these molecules are beginning to have on ion channel biophysics and neuronal physiology.},
  author       = {Mckenzie, Catherine and Sanchez Romero, Inmaculada and Janovjak, Harald L},
  booktitle    = {Novel chemical tools to study ion channel biology},
  isbn         = {978-1-4939-2844-6},
  pages        = {101 -- 117},
  publisher    = {Springer},
  title        = {{Flipping the photoswitch: Ion channels under light control}},
  doi          = {10.1007/978-1-4939-2845-3_6},
  volume       = {869},
  year         = {2015},
}

@article{1550,
  abstract     = {The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.},
  author       = {Mayer, Christian and Jaglin, Xavier and Cobbs, Lucy and Bandler, Rachel and Streicher, Carmen and Cepko, Constance and Hippenmeyer, Simon and Fishell, Gord},
  journal      = {Neuron},
  number       = {5},
  pages        = {989 -- 998},
  publisher    = {Elsevier},
  title        = {{Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries}},
  doi          = {10.1016/j.neuron.2015.07.011},
  volume       = {87},
  year         = {2015},
}

@article{1551,
  abstract     = {Reciprocal coevolution between host and pathogen is widely seen as a major driver of evolution and biological innovation. Yet, to date, the underlying genetic mechanisms and associated trait functions that are unique to rapid coevolutionary change are generally unknown. We here combined experimental evolution of the bacterial biocontrol agent Bacillus thuringiensis and its nematode host Caenorhabditis elegans with large-scale phenotyping, whole genome analysis, and functional genetics to demonstrate the selective benefit of pathogen virulence and the underlying toxin genes during the adaptation process. We show that: (i) high virulence was specifically favoured during pathogen–host coevolution rather than pathogen one-sided adaptation to a nonchanging host or to an environment without host; (ii) the pathogen genotype BT-679 with known nematocidal toxin genes and high virulence specifically swept to fixation in all of the independent replicate populations under coevolution but only some under one-sided adaptation; (iii) high virulence in the BT-679-dominated populations correlated with elevated copy numbers of the plasmid containing the nematocidal toxin genes; (iv) loss of virulence in a toxin-plasmid lacking BT-679 isolate was reconstituted by genetic reintroduction or external addition of the toxins.We conclude that sustained coevolution is distinct from unidirectional selection in shaping the pathogen's genome and life history characteristics. To our knowledge, this study is the first to characterize the pathogen genes involved in coevolutionary adaptation in an animal host–pathogen interaction system.},
  author       = {El Masri, Leila and Branca, Antoine and Sheppard, Anna and Papkou, Andrei and Laehnemann, David and Guenther, Patrick and Prahl, Swantje and Saebelfeld, Manja and Hollensteiner, Jacqueline and Liesegang, Heiko and Brzuszkiewicz, Elzbieta and Daniel, Rolf and Michiels, Nico and Schulte, Rebecca and Kurtz, Joachim and Rosenstiel, Philip and Telschow, Arndt and Bornberg Bauer, Erich and Schulenburg, Hinrich},
  journal      = {PLoS Biology},
  number       = {6},
  pages        = {1 -- 30},
  publisher    = {Public Library of Science},
  title        = {{Host–pathogen coevolution: The selective advantage of Bacillus thuringiensis virulence and its cry toxin genes}},
  doi          = {10.1371/journal.pbio.1002169},
  volume       = {13},
  year         = {2015},
}

@article{1553,
  abstract     = {Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns.},
  author       = {Maiuri, Paolo and Rupprecht, Jean and Wieser, Stefan and Ruprecht, Verena and Bénichou, Olivier and Carpi, Nicolas and Coppey, Mathieu and De Beco, Simon and Gov, Nir and Heisenberg, Carl-Philipp J and Lage Crespo, Carolina and Lautenschlaeger, Franziska and Le Berre, Maël and Lennon Duménil, Ana and Raab, Matthew and Thiam, Hawa and Piel, Matthieu and Sixt, Michael K and Voituriez, Raphaël},
  journal      = {Cell},
  number       = {2},
  pages        = {374 -- 386},
  publisher    = {Cell Press},
  title        = {{Actin flows mediate a universal coupling between cell speed and cell persistence}},
  doi          = {10.1016/j.cell.2015.01.056},
  volume       = {161},
  year         = {2015},
}

@article{1554,
  abstract     = {The visualization of hormonal signaling input and output is key to understanding how multicellular development is regulated. The plant signaling molecule auxin triggers many growth and developmental responses, but current tools lack the sensitivity or precision to visualize these. We developed a set of fluorescent reporters that allow sensitive and semiquantitative readout of auxin responses at cellular resolution in Arabidopsis thaliana. These generic tools are suitable for any transformable plant species.},
  author       = {Liao, Cheyang and Smet, Wouter and Brunoud, Géraldine and Yoshida, Saiko and Vernoux, Teva and Weijers, Dolf},
  journal      = {Nature Methods},
  number       = {3},
  pages        = {207 -- 210},
  publisher    = {Nature Publishing Group},
  title        = {{Reporters for sensitive and quantitative measurement of auxin response}},
  doi          = {10.1038/nmeth.3279},
  volume       = {12},
  year         = {2015},
}

@article{1555,
  abstract     = {We show that incorporating spatial dispersal of individuals into a simple vaccination epidemic model may give rise to a model that exhibits rich dynamical behavior. Using an SIVS (susceptible-infected-vaccinated-susceptible) model as a basis, we describe the spread of an infectious disease in a population split into two regions. In each subpopulation, both forward and backward bifurcations can occur. This implies that for disconnected regions the two-patch system may admit several steady states. We consider traveling between the regions and investigate the impact of spatial dispersal of individuals on the model dynamics. We establish conditions for the existence of multiple nontrivial steady states in the system, and we study the structure of the equilibria. The mathematical analysis reveals an unusually rich dynamical behavior, not normally found in the simple epidemic models. In addition to the disease-free equilibrium, eight endemic equilibria emerge from backward transcritical and saddle-node bifurcation points, forming an interesting bifurcation diagram. Stability of steady states, their bifurcations, and the global dynamics are investigated with analytical tools, numerical simulations, and rigorous set-oriented numerical computations.},
  author       = {Knipl, Diána and Pilarczyk, Pawel and Röst, Gergely},
  issn         = {1536-0040},
  journal      = {SIAM Journal on Applied Dynamical Systems},
  number       = {2},
  pages        = {980 -- 1017},
  publisher    = {Society for Industrial and Applied Mathematics },
  title        = {{Rich bifurcation structure in a two patch vaccination model}},
  doi          = {10.1137/140993934},
  volume       = {14},
  year         = {2015},
}

@article{1556,
  abstract     = {The elongator complex subunit 2 (ELP2) protein, one subunit of an evolutionarily conserved histone acetyltransferase complex, has been shown to participate in leaf patterning, plant immune and abiotic stress responses in Arabidopsis thaliana. Here, its role in root development was explored. Compared to the wild type, the elp2 mutant exhibited an accelerated differentiation of its root stem cells and cell division was more active in its quiescent centre (QC). The key transcription factors responsible for maintaining root stem cell and QC identity, such as AP2 transcription factors PLT1 (PLETHORA1) and PLT2 (PLETHORA2), GRAS transcription factors such as SCR (SCARECROW) and SHR (SHORT ROOT) and WUSCHEL-RELATED HOMEOBOX5 transcription factor WOX5, were all strongly down-regulated in the mutant. On the other hand, expression of the G2/M transition activator CYCB1 was substantially induced in elp2. The auxin efflux transporters PIN1 and PIN2 showed decreased protein levels and PIN1 also displayed mild polarity alterations in elp2, which resulted in a reduced auxin content in the root tip. Either the acetylation or methylation level of each of these genes differed between the mutant and the wild type, suggesting that the ELP2 regulation of root development involves the epigenetic modification of a range of transcription factors and other developmental regulators.},
  author       = {Jia, Yuebin and Tian, Huiyu and Li, Hongjiang and Yu, Qianqian and Wang, Lei and Friml, Jirí and Ding, Zhaojun},
  journal      = {Journal of Experimental Botany},
  number       = {15},
  pages        = {4631 -- 4642},
  publisher    = {Oxford University Press},
  title        = {{The Arabidopsis thaliana elongator complex subunit 2 epigenetically affects root development}},
  doi          = {10.1093/jxb/erv230},
  volume       = {66},
  year         = {2015},
}

@article{1557,
  abstract     = {γ-Aminobutyric acid (GABA)- and glycine-mediated hyperpolarizing inhibition is associated with a chloride influx that depends on the inwardly directed chloride electrochemical gradient. In neurons, the extrusion of chloride from the cytosol primarily depends on the expression of an isoform of potassium-chloride cotransporters (KCC2s). KCC2 is crucial in the regulation of the inhibitory tone of neural circuits, including pain processing neural assemblies. Thus we investigated the cellular distribution of KCC2 in neurons underlying pain processing in the superficial spinal dorsal horn of rats by using high-resolution immunocytochemical methods. We demonstrated that perikarya and dendrites widely expressed KCC2, but axon terminals proved to be negative for KCC2. In single ultrathin sections, silver deposits labeling KCC2 molecules showed different densities on the surface of dendritic profiles, some of which were negative for KCC2. In freeze fracture replicas and tissue sections double stained for the β3-subunit of GABAA receptors and KCC2, GABAA receptors were revealed on dendritic segments with high and also with low KCC2 densities. By measuring the distances between spots immunoreactive for gephyrin (a scaffolding protein of GABAA and glycine receptors) and KCC2 on the surface of neurokinin 1 (NK1) receptor-immunoreactive dendrites, we found that gephyrin-immunoreactive spots were located at various distances from KCC2 cotransporters; 5.7 % of them were recovered in the middle of 4-10-μm-long dendritic segments that were free of KCC2 immunostaining. The variable local densities of KCC2 may result in variable postsynaptic potentials evoked by the activation of GABAA and glycine receptors along the dendrites of spinal neurons.},
  author       = {Javdani, Fariba and Holló, Krisztina and Hegedűs, Krisztina and Kis, Gréta and Hegyi, Zoltán and Dócs, Klaudia and Kasugai, Yu and Fukazawa, Yugo and Shigemoto, Ryuichi and Antal, Miklós},
  journal      = {Journal of Comparative Neurology},
  number       = {13},
  pages        = {1967 -- 1983},
  publisher    = {Wiley-Blackwell},
  title        = {{Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats}},
  doi          = {10.1002/cne.23774},
  volume       = {523},
  year         = {2015},
}

@article{1558,
  abstract     = {CyclophilinAis a conserved peptidyl-prolyl cis-trans isomerase (PPIase) best known as the cellular receptor of the immunosuppressant cyclosporine A. Despite significant effort, evidence of developmental functions of cyclophilin A in non-plant systems has remained obscure. Mutations in a tomato (Solanum lycopersicum) cyclophilin A ortholog, DIAGEOTROPICA (DGT), have been shown to abolish the organogenesis of lateral roots; however, a mechanistic explanation of the phenotype is lacking. Here, we show that the dgt mutant lacks auxin maxima relevant to priming and specification of lateral root founder cells. DGT is expressed in shoot and root, and localizes to both the nucleus and cytoplasm during lateral root organogenesis. Mutation of ENTIRE/ IAA9, a member of the auxin-responsive Aux/IAA protein family of transcriptional repressors, partially restores the inability of dgt to initiate lateral root primordia but not the primordia outgrowth. By comparison, grafting of a wild-type scion restores the process of lateral root formation, consistent with participation of a mobile signal. Antibodies do not detect movement of the DGT protein into the dgt rootstock; however, experiments with radiolabeled auxin and an auxin-specific microelectrode demonstrate abnormal auxin fluxes. Functional studies of DGT in heterologous yeast and tobacco-leaf auxin-transport systems demonstrate that DGT negatively regulates PIN-FORMED (PIN) auxin efflux transporters by affecting their plasma membrane localization. Studies in tomato support complex effects of the dgt mutation on PIN expression level, expression domain and plasma membrane localization. Our data demonstrate that DGT regulates auxin transport in lateral root formation.},
  author       = {Ivanchenko, Maria and Zhu, Jinsheng and Wang, Bangjun and Medvecka, Eva and Du, Yunlong and Azzarello, Elisa and Mancuso, Stefano and Megraw, Molly and Filichkin, Sergei and Dubrovsky, Joseph and Friml, Jirí and Geisler, Markus},
  journal      = {Development},
  number       = {4},
  pages        = {712 -- 721},
  publisher    = {Company of Biologists},
  title        = {{The cyclophilin a DIAGEOTROPICA gene affects auxin transport in both root and shoot to control lateral root formation}},
  doi          = {10.1242/dev.113225},
  volume       = {142},
  year         = {2015},
}

@article{1559,
  abstract     = {There are deep, yet largely unexplored, connections between computer science and biology. Both disciplines examine how information proliferates in time and space. Central results in computer science describe the complexity of algorithms that solve certain classes of problems. An algorithm is deemed efficient if it can solve a problem in polynomial time, which means the running time of the algorithm is a polynomial function of the length of the input. There are classes of harder problems for which the fastest possible algorithm requires exponential time. Another criterion is the space requirement of the algorithm. There is a crucial distinction between algorithms that can find a solution, verify a solution, or list several distinct solutions in given time and space. The complexity hierarchy that is generated in this way is the foundation of theoretical computer science. Precise complexity results can be notoriously difficult. The famous question whether polynomial time equals nondeterministic polynomial time (i.e., P = NP) is one of the hardest open problems in computer science and all of mathematics. Here, we consider simple processes of ecological and evolutionary spatial dynamics. The basic question is: What is the probability that a new invader (or a new mutant)will take over a resident population?We derive precise complexity results for a variety of scenarios. We therefore show that some fundamental questions in this area cannot be answered by simple equations (assuming that P is not equal to NP).},
  author       = {Ibsen-Jensen, Rasmus and Chatterjee, Krishnendu and Nowak, Martin},
  journal      = {PNAS},
  number       = {51},
  pages        = {15636 -- 15641},
  publisher    = {National Academy of Sciences},
  title        = {{Computational complexity of ecological and evolutionary spatial dynamics}},
  doi          = {10.1073/pnas.1511366112},
  volume       = {112},
  year         = {2015},
}

