@inbook{1443, abstract = {Here we survey several results and conjectures on the cohomology of the total space of the Hitchin system: the moduli space of semi-stable rank n and degree d Higgs bundles on a complex algebraic curve C. The picture emerging is a dynamic mixture of ideas originating in theoretical physics such as gauge theory and mirror symmetry, Weil conjectures in arithmetic algebraic geometry, representation theory of finite groups of Lie type and Langlands duality in number theory.}, author = {Tamas Hausel}, booktitle = {Handbook of Moduli: Volume II}, pages = {29 -- 70}, publisher = {International Press}, title = {{Global topology of the Hitchin system}}, volume = {25}, year = {2013}, } @article{1469, abstract = {We study connections between the topology of generic character varieties of fundamental groups of punctured Riemann surfaces, Macdonald polynomials, quiver representations, Hilbert schemes on Cx × Cx, modular forms and multiplicities in tensor products of irreducible characters of finite general linear groups.}, author = {Tamas Hausel and Letellier, Emmanuel and Rodríguez Villegas, Fernando}, journal = {Advances in Mathematics}, pages = {85 -- 128}, publisher = {Academic Press}, title = {{Arithmetic harmonic analysis on character and quiver varieties II}}, doi = {10.1016/j.aim.2012.10.009}, volume = {234}, year = {2013}, } @article{1470, abstract = {We show that a natural isomorphism between the rational cohomology groups of the two zero-dimensional Hilbert schemes of n-points of two surfaces, the affine plane minus the axes and the cotangent bundle of an elliptic curve, exchanges the weight filtration on the first set of cohomology groups with the perverse Leray filtration associated with a natural fibration on the second set of cohomology groups. We discuss some associated hard Lefschetz phenomena.}, author = {De Cataldo, Mark A and Tamas Hausel and Migliorini, Luca}, journal = {Journal of Singularities}, pages = {23 -- 38}, publisher = {Worldwide Center of Mathematics}, title = {{Exchange between perverse and weight filtration for the Hilbert schemes of points of two surfaces}}, doi = {10.5427/jsing.2013.7c}, volume = {7}, year = {2013}, } @article{15162, abstract = {Cytological profiling (CP) is an unbiased image-based screening technique that uses automated microscopy and image analysis to profile compounds based on numerous quantifiable phenotypic features. We used CP to evaluate a library of nearly 500 compounds with documented mechanisms of action (MOAs) spanning a wide range of biological pathways. We developed informatics techniques for generating dosage-independent phenotypic “fingerprints” for each compound, and for quantifying the likelihood that a compound's CP fingerprint corresponds to its annotated MOA. We identified groups of features that distinguish classes with closely related phenotypes, such as microtubule poisons vs. HSP90 inhibitors, and DNA synthesis vs. proteasome inhibitors. We tested several cases in which cytological profiles indicated novel mechanisms, including a tyrphostin kinase inhibitor involved in mitochondrial uncoupling, novel microtubule poisons, and a nominal PPAR-gamma ligand that acts as a proteasome inhibitor, using independent biochemical assays to confirm the MOAs predicted by the CP signatures. We also applied maximal-information statistics to identify correlations between cytological features and kinase inhibitory activities by combining the CP fingerprints of 24 kinase inhibitors with published data on their specificities against a diverse panel of kinases. The resulting analysis suggests a strategy for probing the biological functions of specific kinases by compiling cytological data from inhibitors of varying specificities.}, author = {Woehrmann, Marcos H. and Bray, Walter M. and Durbin, James K. and Nisam, Sean C. and Michael, Alicia Kathleen and Glassey, Emerson and Stuart, Joshua M. and Lokey, R. Scott}, issn = {1742-2051}, journal = {Molecular BioSystems}, keywords = {Molecular Biology, Biotechnology}, number = {11}, publisher = {Royal Society of Chemistry}, title = {{Large-scale cytological profiling for functional analysis of bioactive compounds}}, doi = {10.1039/c3mb70245f}, volume = {9}, year = {2013}, } @article{1977, abstract = {Complex I (NADH:ubiquinone oxidoreductase) is central to cellular energy production, being the first and largest enzyme of the respiratory chain in mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the inner mitochondrial membrane and is involved in a wide range of human neurodegenerative disorders. Mammalian complex I is composed of 44 different subunits, whereas the 'minimal' bacterial version contains 14 highly conserved 'core' subunits. The L-shaped assembly consists of hydrophilic and membrane domains. We have determined all known atomic structures of complex I, starting from the hydrophilic domain of Thermus thermophilus enzyme (eight subunits, nine Fe-S clusters), followed by the membrane domains of the Escherichia coli (six subunits, 55 transmembrane helices) and T. thermophilus (seven subunits, 64 transmembrane helices) enzymes, and finally culminating in a recent crystal structure of the entire intact complex I from T. thermophilus (536 kDa, 16 subunits, nine Fe-S clusters, 64 transmembrane helices). The structure suggests an unusual and unique coupling mechanism via longrange conformational changes. Determination of the structure of the entire complex was possible only through this step-by-step approach, building on from smaller subcomplexes towards the entire assembly. Large membrane proteins are notoriously difficult to crystallize, and so various non-standard and sometimes counterintuitive approaches were employed in order to achieve crystal diffraction to high resolution and solve the structures. These steps, as well as the implications from the final structure, are discussed in the present review.}, author = {Leonid Sazanov and Baradaran, Rozbeh and Efremov, Rouslan G and Berrisford, John M and Minhas, Gurdeep S}, journal = {Biochemical Society Transactions}, number = {5}, pages = {1265 -- 1271}, publisher = {Portland Press}, title = {{A long road towards the structure of respiratory complex I, a giant molecular proton pump}}, doi = {10.1042/BST20130193}, volume = {41}, year = {2013}, } @article{476, abstract = {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. }, author = {Dickerson, Desiree and Bilkey, David}, journal = {Frontiers in Behavioral Neuroscience}, number = {DEC}, publisher = {Frontiers Research Foundation}, title = {{Aberrant neural synchrony in the maternal immune activation model: Using translatable measures to explore targeted interventions}}, doi = {10.3389/fnbeh.2013.00217}, volume = {7}, year = {2013}, } @article{499, abstract = {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.}, author = {Wakamoto, Yurichi and Dhar, Neraaj and Chait, Remy P and Schneider, Katrin and Signorino Gelo, François and Leibler, Stanislas and Mckinney, John}, journal = {Science}, number = {6115}, pages = {91 -- 95}, publisher = {American Association for the Advancement of Science}, title = {{Dynamic persistence of antibiotic-stressed mycobacteria}}, doi = {10.1126/science.1229858}, volume = {339}, year = {2013}, } @article{500, abstract = {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.}, author = {Ward, Melissa and Lycett, Samantha and Avila, Dorita and Bollback, Jonathan P and Leigh Brown, Andrew}, journal = {BMC Evolutionary Biology}, number = {1}, publisher = {BioMed Central}, title = {{Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza}}, doi = {10.1186/1471-2148-13-222}, volume = {13}, year = {2013}, } @article{501, abstract = {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.}, author = {Cozzuol, Mario and Clozato, Camila and Holanda, Elizete and Rodrigues, Flávio and Nienow, Samuel and De Thoisy, Benoit and Fernandes Redondo, Rodrigo A and Santos, Fabrício}, journal = {Journal of Mammalogy}, number = {6}, pages = {1331 -- 1345}, publisher = {Oxford University Press}, title = {{A new species of tapir from the Amazon}}, doi = {10.1644/12-MAMM-A-169.1}, volume = {94}, year = {2013}, } @article{502, abstract = {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. }, author = {Blazy, Olivier and Fuchsbauer, Georg and Pointcheval, David and Vergnaud, Damien}, journal = {Journal of Computer Security}, number = {5}, pages = {627 -- 661}, publisher = {IOS Press}, title = {{Short blind signatures}}, doi = {10.3233/JCS-130477}, volume = {21}, year = {2013}, } @article{505, abstract = {Alkyd resins are polyesters containing unsaturated fatty acids that are used as binding agents in paints and coatings. Chemical drying of these polyesters is based on heavy metal catalyzed cross-linking of the unsaturated fatty acid moieties. Among the heavy-metal catalysts, cobalt complexes are the most effective, yet they have been proven to be carcinogenic. Therefore, strategies to replace the cobalt-based catalyst by environmentally friendlier and less toxic alternatives are under development. Here, we demonstrate for the first time that a laccase-mediator system can effectively replace the heavy-metal catalyst and cross-link alkyd resins. Interestingly, the biocatalytic reaction does not only work in aqueous media, but also in a solid film, where enzyme diffusion is limited. Within the catalytic cycle, the mediator oxidizes the alkyd resin and is regenerated by the laccase, which is uniformly distributed within the drying film as evidenced by confocal laser scanning microscopy. During gradual build-up of molecular weight, there is a concomitant decrease of the oxygen content in the film. A new optical sensor to follow oxygen consumption during the cross-linking reaction was developed and validated with state of the art techniques. A remarkable feature is the low sample amount required, which allows faster screening of new catalysts.}, author = {Greimel, Katrin and Perz, Veronika and Koren, Klaus and Feola, Roland and Temel, Armin and Sohar, Christian and Herrero Acero, Enrique and Klimant, Ingo and Guebitz, Georg}, journal = {Green Chemistry}, number = {2}, pages = {381 -- 388}, publisher = {Royal Society of Chemistry}, title = {{Banning toxic heavy-metal catalysts from paints: Enzymatic cross-linking of alkyd resins}}, doi = {10.1039/c2gc36666e}, volume = {15}, year = {2013}, } @article{507, abstract = {Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4- (4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.}, author = {Kim, Soo and Xu, Zheng and Song, Kyungyoung and Kim, Dae and Kang, Hyangju and Reichardt, Ilka and Sohn, Eun and Friml, Jirí and Juergens, Gerd and Hwang, Inhwan}, journal = {Plant Cell}, number = {8}, pages = {2970 -- 2985}, publisher = {American Society of Plant Biologists}, title = {{Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive organ development in arabidopsis}}, doi = {10.1105/tpc.113.114264}, volume = {25}, year = {2013}, } @article{508, abstract = {The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.}, author = {Tarazona Santos, Eduardo and Machado, Moara and Magalhães, Wagner and Chen, Renee and Lyon, Fernanda and Burdett, Laurie and Crenshaw, Andrew and Fabbri, Cristina and Pereira, Latife and Pinto, Laelia and Fernandes Redondo, Rodrigo A and Sestanovich, Ben and Yeager, Meredith and Chanock, Stephen}, journal = {Molecular Biology and Evolution}, number = {9}, pages = {2157 -- 2167}, publisher = {Oxford University Press}, title = {{Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications}}, doi = {10.1093/molbev/mst119}, volume = {30}, year = {2013}, } @article{509, abstract = {Clathrin-mediated endocytosis (CME) regulates many aspects of plant development, including hormone signaling and responses to environmental stresses. Despite the importance of this process, the machinery that regulates CME in plants is largely unknown. In mammals, the heterotetrameric ADAPTOR PROTEIN COMPLEX-2 (AP-2) is required for the formation of clathrin-coated vesicles at the plasma membrane (PM). Although the existence of AP-2 has been predicted in Arabidopsis thaliana, the biochemistry and functionality of the complex is still uncharacterized. Here, we identified all the subunits of the Arabidopsis AP-2 by tandem affinity purification and found that one of the large AP-2 subunits, AP2A1, localized at the PM and interacted with clathrin. Furthermore, endocytosis of the leucine-rich repeat receptor kinase, BRASSINOSTEROID INSENSITIVE1 (BRI1), was shown to depend on AP-2. Knockdown of the two Arabidopsis AP2A genes or overexpression of a dominant-negative version of the medium AP-2 subunit, AP2M, impaired BRI1 endocytosis and enhanced the brassinosteroid signaling. Our data reveal that the CME machinery in Arabidopsis is evolutionarily conserved and that AP-2 functions in receptormediated endocytosis. }, author = {Di Rubbo, Simone and Irani, Niloufer and Kim, Soo and Xu, Zheng and Gadeyne, Astrid and Dejonghe, Wim and Vanhoutte, Isabelle and Persiau, Geert and Eeckhout, Dominique and Simon, Sibu and Song, Kyungyoung and Kleine Vehn, Jürgen and Friml, Jirí and De Jaeger, Geert and Van Damme, Daniël and Hwang, Inhwan and Russinova, Eugenia}, journal = {Plant Cell}, number = {8}, pages = {2986 -- 2997}, publisher = {American Society of Plant Biologists}, title = {{The clathrin adaptor complex AP-2 mediates endocytosis of brassinosteroid INSENSITIVE1 in arabidopsis}}, doi = {10.1105/tpc.113.114058}, volume = {25}, year = {2013}, } @article{511, abstract = {The native auxin, indole-3-acetic acid (IAA), is a major regulator of plant growth and development. Its nonuniform distribution between cells and tissues underlies the spatiotemporal coordination of many developmental events and responses to environmental stimuli. The regulation of auxin gradients and the formation of auxin maxima/minima most likely involve the regulation of both metabolic and transport processes. In this article, we have demonstrated that 2-oxindole-3-acetic acid (oxIAA) is a major primary IAA catabolite formed in Arabidopsis thaliana root tissues. OxIAA had little biological activity and was formed rapidly and irreversibly in response to increases in auxin levels. We further showed that there is cell type-specific regulation of oxIAA levels in the Arabidopsis root apex. We propose that oxIAA is an important element in the regulation of output from auxin gradients and, therefore, in the regulation of auxin homeostasis and response mechanisms.}, author = {Pěnčík, Aleš and Simonovik, Biljana and Petersson, Sara and Henyková, Eva and Simon, Sibu and Greenham, Kathleen and Zhang, Yi and Kowalczyk, Mariusz and Estelle, Mark and Zažímalová, Eva and Novák, Ondřej and Sandberg, Göran and Ljung, Karin}, journal = {Plant Cell}, number = {10}, pages = {3858 -- 3870}, publisher = {American Society of Plant Biologists}, title = {{Regulation of auxin homeostasis and gradients in Arabidopsis roots through the formation of the indole-3-acetic acid catabolite 2-oxindole-3-acetic acid}}, doi = {10.1105/tpc.113.114421}, volume = {25}, year = {2013}, } @article{516, abstract = {In plants, changes in local auxin concentrations can trigger a range of developmental processes as distinct tissues respond differently to the same auxin stimulus. However, little is known about how auxin is interpreted by individual cell types. We performed a transcriptomic analysis of responses to auxin within four distinct tissues of the Arabidopsis thaliana root and demonstrate that different cell types show competence for discrete responses. The majority of auxin‐responsive genes displayed a spatial bias in their induction or repression. The novel data set was used to examine how auxin influences tissue‐specific transcriptional regulation of cell‐identity markers. Additionally, the data were used in combination with spatial expression maps of the root to plot a transcriptomic auxin‐response gradient across the apical and basal meristem. The readout revealed a strong correlation for thousands of genes between the relative response to auxin and expression along the longitudinal axis of the root. This data set and comparative analysis provide a transcriptome‐level spatial breakdown of the response to auxin within an organ where this hormone mediates many aspects of development.}, author = {Bargmann, Bastiaan and Vanneste, Steffen and Krouk, Gabriel and Nawy, Tal and Efroni, Idan and Shani, Eilon and Choe, Goh and Friml, Jirí and Bergmann, Dominique and Estelle, Mark and Birnbaum, Kenneth}, journal = {Molecular Systems Biology}, number = {1}, publisher = {Nature Publishing Group}, title = {{A map of cell type‐specific auxin responses}}, doi = {10.1038/msb.2013.40}, volume = {9}, year = {2013}, } @article{522, abstract = {Podoplanin, a mucin-like plasma membrane protein, is expressed by lymphatic endothelial cells and responsible for separation of blood and lymphatic circulation through activation of platelets. Here we show that podoplanin is also expressed by thymic fibroblastic reticular cells (tFRC), a novel thymic medulla stroma cell type associated with thymic conduits, and involved in development of natural regulatory T cells (nTreg). Young mice deficient in podoplanin lack nTreg owing to retardation of CD4+CD25+ thymocytes in the cortex and missing differentiation of Foxp3+ thymocytes in the medulla. This might be due to CCL21 that delocalizes upon deletion of the CCL21-binding podoplanin from medullar tFRC to cortex areas. The animals do not remain devoid of nTreg but generate them delayed within the first month resulting in Th2-biased hypergammaglobulinemia but not in the death-causing autoimmune phenotype of Foxp3-deficient Scurfy mice.}, author = {Fuertbauer, Elke and Zaujec, Jan and Uhrin, Pavel and Raab, Ingrid and Weber, Michele and Schachner, Helga and Bauer, Miroslav and Schütz, Gerhard and Binder, Bernd and Sixt, Michael K and Kerjaschki, Dontscho and Stockinger, Hannes}, journal = {Immunology Letters}, number = {1-2}, pages = {31 -- 41}, publisher = {Elsevier}, title = {{Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells}}, doi = {10.1016/j.imlet.2013.07.007}, volume = {154}, year = {2013}, } @article{527, abstract = {The apical-basal axis of the early plant embryo determines the body plan of the adult organism. To establish a polarized embryonic axis, plants evolved a unique mechanism that involves directional, cell-to-cell transport of the growth regulator auxin. Auxin transport relies on PIN auxin transporters [1], whose polar subcellular localization determines the flow directionality. PIN-mediated auxin transport mediates the spatial and temporal activity of the auxin response machinery [2-7] that contributes to embryo patterning processes, including establishment of the apical (shoot) and basal (root) embryo poles [8]. However, little is known of upstream mechanisms guiding the (re)polarization of auxin fluxes during embryogenesis [9]. Here, we developed a model of plant embryogenesis that correctly generates emergent cell polarities and auxin-mediated sequential initiation of apical-basal axis of plant embryo. The model relies on two precisely localized auxin sources and a feedback between auxin and the polar, subcellular PIN transporter localization. Simulations reproduced PIN polarity and auxin distribution, as well as previously unknown polarization events during early embryogenesis. The spectrum of validated model predictions suggests that our model corresponds to a minimal mechanistic framework for initiation and orientation of the apical-basal axis to guide both embryonic and postembryonic plant development.}, author = {Wabnik, Krzysztof T and Robert, Hélène and Smith, Richard and Friml, Jirí}, journal = {Current Biology}, number = {24}, pages = {2513 -- 2518}, publisher = {Cell Press}, title = {{Modeling framework for the establishment of the apical-basal embryonic axis in plants}}, doi = {10.1016/j.cub.2013.10.038}, volume = {23}, year = {2013}, } @article{528, abstract = {Establishment of the embryonic axis foreshadows the main body axis of adults both in plants and in animals, but underlying mechanisms are considered distinct. Plants utilize directional, cell-to-cell transport of the growth hormone auxin [1, 2] to generate an asymmetric auxin response that specifies the embryonic apical-basal axis [3-6]. The auxin flow directionality depends on the polarized subcellular localization of PIN-FORMED (PIN) auxin transporters [7, 8]. It remains unknown which mechanisms and spatial cues guide cell polarization and axis orientation in early embryos. Herein, we provide conceptually novel insights into the formation of embryonic axis in Arabidopsis by identifying a crucial role of localized tryptophan-dependent auxin biosynthesis [9-12]. Local auxin production at the base of young embryos and the accompanying PIN7-mediated auxin flow toward the proembryo are required for the apical auxin response maximum and the specification of apical embryonic structures. Later in embryogenesis, the precisely timed onset of localized apical auxin biosynthesis mediates PIN1 polarization, basal auxin response maximum, and specification of the root pole. Thus, the tight spatiotemporal control of distinct local auxin sources provides a necessary, non-cell-autonomous trigger for the coordinated cell polarization and subsequent apical-basal axis orientation during embryogenesis and, presumably, also for other polarization events during postembryonic plant life [13, 14].}, author = {Robert, Hélène and Grones, Peter and Stepanova, Anna and Robles, Linda and Lokerse, Annemarie and Alonso, Jose and Weijers, Dolf and Friml, Jirí}, journal = {Current Biology}, number = {24}, pages = {2506 -- 2512}, publisher = {Cell Press}, title = {{Local auxin sources orient the apical basal axis in arabidopsis embryos}}, doi = {10.1016/j.cub.2013.09.039}, volume = {23}, year = {2013}, } @misc{5399, abstract = {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.}, author = {Reiter, Johannes and Bozic, Ivana and Chatterjee, Krishnendu and Nowak, Martin}, issn = {2664-1690}, pages = {17}, publisher = {IST Austria}, title = {{TTP: Tool for Tumor Progression}}, doi = {10.15479/AT:IST-2013-104-v1-1}, year = {2013}, }