@article{3090, abstract = {The polarized transport of the phytohormone auxin [1], which is crucial for the regulation of different stages of plant development [2, 3], depends on the asymmetric plasma membrane distribution of the PIN-FORMED (PIN) auxin efflux carriers [4, 5]. The PIN polar localization results from clathrin-mediated endocytosis (CME) from the plasma membrane and subsequent polar recycling [6]. The Arabidopsis genome encodes two groups of dynamin-related proteins (DRPs) that show homology to mammalian dynamin - a protein required for fission of endocytic vesicles during CME [7, 8]. Here we show by coimmunoprecipitation (coIP), bimolecular fluorescence complementation (BiFC), and Förster resonance energy transfer (FRET) that members of the DRP1 group closely associate with PIN proteins at the cell plate. Localization and phenotypic analysis of novel drp1 mutants revealed a requirement for DRP1 function in correct PIN distribution and in auxin-mediated development. We propose that rapid and specific internalization of PIN proteins mediated by the DRP1 proteins and the associated CME machinery from the cell plate membranes during cytokinesis is an important mechanism for proper polar PIN positioning in interphase cells.}, author = {Mravec, Jozef and Petrášek, Jan and Li, Na and Boeren, Sjef and Karlova, Rumyana and Kitakura, Saeko and Pařezová, Markéta and Naramoto, Satoshi and Nodzyński, Thomasz and Dhonukshe, Pankaj and Bednarek, Sebastian Y and Zažímalová, Eva and De Vries, Sacco and Jirí Friml}, journal = {Current Biology}, number = {12}, pages = {1055 -- 1060}, publisher = {Cell Press}, title = {{Cell plate restricted association of DRP1A and PIN proteins is required for cell polarity establishment in arabidopsis}}, doi = {10.1016/j.cub.2011.05.018}, volume = {21}, year = {2011}, } @article{3091, author = {Sauer, Michael and Friml, Jirí}, journal = {Molecular Systems Biology}, publisher = {Nature Publishing Group}, title = {{Fleeting hormone cues get stabilized for plant organogenesis}}, doi = {10.1038/msb.2011.45}, volume = {7}, year = {2011}, } @article{3092, abstract = {The phytohormone auxin is vital to plant growth and development. A unique property of auxin among all other plant hormones is its cell-to-cell polar transport that requires activity of polarly localized PIN-FORMED (PIN) auxin efflux transporters. Despite the substantial molecular insight into the cellular PIN polarization, the mechanistic understanding for developmentally and environmentally regulated PIN polarization is scarce. The long-standing belief that auxin modulates its own transport by means of a positive feedback mechanism has inspired both experimentalists and theoreticians for more than two decades. Recently, theoretical models for auxin-dependent patterning in plants include the feedback between auxin transport and the PIN protein localization. These computer models aid to assess the complexity of plant development by testing and predicting plausible scenarios for various developmental processes that occur in planta. Although the majority of these models rely on purely heuristic principles, the most recent mechanistic models tentatively integrate biologically testable components into known cellular processes that underlie the PIN polarity regulation. The existing and emerging computational approaches to describe PIN polarization are presented and discussed in the light of recent experimental data on the PIN polar targeting.}, author = {Wabnik, Krzysztof T and Govaerts, Willy and Friml, Jirí and Kleine Vehn, Jürgen}, journal = {Molecular BioSystems}, number = {8}, pages = {2352 -- 2359}, publisher = {Royal Society of Chemistry}, title = {{Feedback models for polarized auxin transport: An emerging trend}}, doi = {10.1039/c1mb05109a}, volume = {7}, year = {2011}, } @article{3093, abstract = { Plants take up iron from the soil using the IRON-REGULATED TRANSPORTER 1 (IRT1) high-affinity iron transporter at the root surface. Sophisticated regulatory mechanisms allow plants to tightly control the levels of IRT1, ensuring optimal absorption of essential but toxic iron. Here, we demonstrate that overexpression of Arabidopsis thaliana IRT1 leads to constitutive IRT1 protein accumulation, metal overload, and oxidative stress. IRT1 is unexpectedly found in trans-Golgi network/early endosomes of root hair cells, and its levels and localization are unaffected by iron nutrition. Using pharmacological approaches, we show that IRT1 cycles to the plasma membrane to perform iron and metal uptake at the cell surface and is sent to the vacuole for proper turnover. We also prove that IRT1 is monoubiquitinated on several cytosol-exposed residues in vivo and that mutation of two putative monoubiquitination target residues in IRT1 triggers stabilization at the plasma membrane and leads to extreme lethality. Together, these data suggest a model in which monoubiquitin-dependent internalization/sorting and turnover keep the plasma membrane pool of IRT1 low to ensure proper iron uptake and to prevent metal toxicity. More generally, our work demonstrates the existence of monoubiquitin-dependent trafficking to lytic vacuoles in plants and points to proteasome-independent turnover of plasma membrane proteins.}, author = {Barberon, Marie and Zelazny, Enric and Robert, Stéphanie and Conéjéro, Geneviève and Curie, Cathy and Jirí Friml and Vert, Grégory}, journal = {PNAS}, number = {32}, pages = {E450 -- E458}, publisher = {National Academy of Sciences}, title = {{Monoubiquitin dependent endocytosis of the Iron Regulated Transporter 1 IRT1 transporter controls iron uptake in plants}}, doi = {10.1073/pnas.1100659108}, volume = {108}, year = {2011}, } @article{3094, abstract = {Summary Gravitropism aligns plant growth with gravity. It involves gravity perception and the asymmetric distribution of the phytohormone auxin. Here we provide insights into the mechanism for hypocotyl gravitropic growth. We show that the Arabidopsis thaliana PIN3 auxin transporter is required for the asymmetric auxin distribution for the gravitropic response. Gravistimulation polarizes PIN3 to the bottom side of hypocotyl endodermal cells, which correlates with an increased auxin response at the lower hypocotyl side. Both PIN3 polarization and hypocotyl bending require the activity of the trafficking regulator GNOM and the protein kinase PINOID. Our data suggest that gravity-induced PIN3 polarization diverts the auxin flow to mediate the asymmetric distribution of auxin for gravitropic shoot bending.}, author = {Rakusová, Hana and Gallego-Bartolomé, Javier and Vanstraelen, Marleen and Robert, Hélène S and Alabadí, David and Blázquez, Miguel A and Eva Benková and Jirí Friml}, journal = {Plant Journal}, number = {5}, pages = {817 -- 826}, publisher = {Wiley-Blackwell}, title = {{Polarization of PIN3 dependent auxin transport for hypocotyl gravitropic response in Arabidopsis thaliana}}, doi = {10.1111/j.1365-313X.2011.04636.x}, volume = {67}, year = {2011}, } @article{3095, abstract = {Root system architecture depends on lateral root (LR) initiation that takes place in a relatively narrow developmental window (DW). Here, we analyzed the role of auxin gradients established along the parent root in defining this DW for LR initiation. Correlations between auxin distribution and response, and spatiotemporal control of LR initiation were analyzed in Arabidopsis thaliana and tomato (Solanum lycopersicum). In both Arabidopsis and tomato roots, a well defined zone, where auxin content and response are minimal, demarcates the position of a DW for founder cell specification and LR initiation. We show that in the zone of auxin minimum pericycle cells have highest probability to become founder cells and that auxin perception via the TIR1/AFB pathway, and polar auxin transport, are essential for the establishment of this zone. Altogether, this study reveals that the same morphogen-like molecule, auxin, can act simultaneously as a morphogenetic trigger of LR founder cell identity and as a gradient-dependent signal defining positioning of the founder cell specification. This auxin minimum zone might represent an important control mechanism ensuring the LR initiation steadiness and the acropetal LR initiation pattern. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.}, author = {Dubrovsky, Joseph G and Napsucialy-Mendivil, Selene and Duclercq, Jérôme and Cheng, Yan and Shishkova, Svetlana O and Ivanchenko, Maria G and Jirí Friml and Murphy, Angus S and Eva Benková}, journal = {New Phytologist}, number = {4}, pages = {970 -- 983}, publisher = {Wiley-Blackwell}, title = {{Auxin minimum defines a developmental window for lateral root initiation}}, doi = { 10.1111/j.1469-8137.2011.03757.x}, volume = {191}, year = {2011}, } @article{3096, abstract = {Carrier-dependent, intercellular auxin transport is central to the developmental patterning of higher plants (tracheophytes). The evolution of this polar auxin transport might be linked to the translocation of some PIN auxin efflux carriers from their presumably ancestral localization at the endoplasmic reticulum (ER) to the polar domains at the plasma membrane. Here we propose an eventually ancient mechanism of intercellular auxin distribution by ER-localized auxin transporters involving intracellular auxin retention and switch-like release from the ER. The proposed model integrates feedback circuits utilizing the conserved nuclear auxin signaling for the regulation of PIN transcription and a hypothetical ER-based signaling for the regulation of PIN-dependent transport activity at the ER. Computer simulations of the model revealed its plausibility for generating auxin channels and localized auxin maxima highlighting the possibility of this alternative mechanism for polar auxin transport.}, author = {Wabnik, Krzysztof T and Kleine Vehn, Jürgen and Govaerts, Willy and Friml, Jirí}, journal = {Trends in Plant Science}, number = {9}, pages = {468 -- 475}, publisher = {Cell Press}, title = {{Prototype cell-to-cell auxin transport mechanism by intracellular auxin compartmentalization}}, doi = {10.1016/j.tplants.2011.05.002}, volume = {16}, year = {2011}, } @article{3097, abstract = {Cytokinin is an important regulator of plant growth and development. In Arabidopsis thaliana, the two-component phosphorelay mediated through a family of histidine kinases and response regulators is recognized as the principal cytokinin signal transduction mechanism activating the complex transcriptional response to control various developmental processes. Here, we identified an alternative mode of cytokinin action that uses endocytic trafficking as a means to direct plant organogenesis. This activity occurs downstream of known cytokinin receptors but through a branch of the cytokinin signaling pathway that does not involve transcriptional regulation. We show that cytokinin regulates endocytic recycling of the auxin efflux carrier PINFORMED1 (PIN1) by redirecting it for lytic degradation in vacuoles. Stimulation of the lytic PIN1 degradation is not a default effect for general downregulation of proteins from plasma membranes, but a specific mechanism to rapidly modulate the auxin distribution in cytokinin-mediated developmental processes.}, author = {Peter Marhavy and Bielach, Agnieszka and Abas, Lindy and Abuzeineh, Anas and Duclercq, Jérôme and Tanaka, Hirokazu and Pařezová, Markéta and Petrášek, Jan and Jirí Friml and Kleine-Vehn, Jürgen and Eva Benková}, journal = {Developmental Cell}, number = {4}, pages = {796 -- 804}, publisher = {Cell Press}, title = {{Cytokinin modulates endocytic trafficking of PIN1 auxin efflux carrier to control plant organogenesis}}, doi = {10.1016/j.devcel.2011.08.014}, volume = {21}, year = {2011}, } @article{3098, abstract = {Cell polarity reflected by asymmetric distribution of proteins at the plasma membrane is a fundamental feature of unicellular and multicellular organisms. It remains conceptually unclear how cell polarity is kept in cell wall-encapsulated plant cells. We have used super-resolution and semi-quantitative live-cell imaging in combination with pharmacological, genetic, and computational approaches to reveal insights into the mechanism of cell polarity maintenance in Arabidopsis thaliana. We show that polar-competent PIN transporters for the phytohormone auxin are delivered to the center of polar domains by super-polar recycling. Within the plasma membrane, PINs are recruited into non-mobile membrane clusters and their lateral diffusion is dramatically reduced, which ensures longer polar retention. At the circumventing edges of the polar domain, spatially defined internalization of escaped cargos occurs by clathrin-dependent endocytosis. Computer simulations confirm that the combination of these processes provides a robust mechanism for polarity maintenance in plant cells. Moreover, our study suggests that the regulation of lateral diffusion and spatially defined endocytosis, but not super-polar exocytosis have primary importance for PIN polarity maintenance.}, author = {Kleine-Vehn, Jürgen and Krzysztof Wabnik and Martinière, Alexandre and Łangowski, Łukasz and Willig, Katrin and Naramoto, Satoshi and Leitner, Johannes and Tanaka, Hirokazu and Jakobs, Stefan and Robert, Stéphanie and Luschnig, Christian and Govaerts, Willy J and Hell, Stefan W and Runions, John and Jirí Friml}, journal = {Molecular Systems Biology}, publisher = {Nature Publishing Group}, title = {{Recycling, clustering and endocytosis jointly maintain PIN auxin carrier polarity at the plasma membrane}}, doi = {10.1038/msb.2011.72}, volume = {7}, year = {2011}, } @article{3099, abstract = {Endomembrane trafficking relies on the coordination of a highly complex, dynamic network of intracellular vesicles. Understanding the network will require a dissection of cargo and vesicle dynamics at the cellular level in vivo. This is also a key to establishing a link between vesicular networks and their functional roles in development. We used a high-content intracellular screen to discover small molecules targeting endomembrane trafficking in vivo in a complex eukaryote, Arabidopsis thaliana. Tens of thousands of molecules were prescreened and a selected subset was interrogated against a panel of plasma membrane (PM) and other endomembrane compartment markers to identify molecules that altered vesicle trafficking. The extensive image dataset was transformed by a flexible algorithm into a marker-by-phenotype-by-treatment time matrix and revealed groups of molecules that induced similar subcellular fingerprints (clusters). This matrix provides a platform for a systems view of trafficking. Molecules from distinct clusters presented avenues and enabled an entry point to dissect recycling at the PM, vacuolar sorting, and cell-plate maturation. Bioactivity in human cells indicated the value of the approach to identifying small molecules that are active in diverse organisms for biology and drug discovery.}, author = {Drakakaki, Georgia and Robert, Stéphanie and Szatmári, Anna-Maria and Brown, Michelle Q and Nagawa, Shingo and Van Damme, Daniël and Leonard, Marylin and Yang, Zhenbiao and Girke, Thomas and Schmid, Sandra L and Russinova, Eugenia and Jirí Friml and Raikhel, Natasha V and Hicks, Glen R}, journal = {PNAS}, number = {43}, pages = {17850 -- 17855}, publisher = {National Academy of Sciences}, title = {{Clusters of bioactive compounds target dynamic endomembrane networks in vivo}}, doi = {10.1073/pnas.1108581108}, volume = {108}, year = {2011}, } @article{3100, abstract = {In multicellular organisms, morphogenesis relies on a strict coordination in time and space of cell proliferation and differentiation. In contrast to animals, plant development displays continuous organ formation and adaptive growth responses during their lifespan relying on a tight coordination of cell proliferation. How developmental signals interact with the plant cell-cycle machinery is largely unknown. Here, we characterize plant A2-type cyclins, a small gene family of mitotic cyclins, and show how they contribute to the fine-tuning of local proliferation during plant development. Moreover, the timely repression of CYCA2;3 expression in newly formed guard cells is shown to require the stomatal transcription factors FOUR LIPS/MYB124 and MYB88, providing a direct link between developmental programming and cell-cycle exit in plants. Thus, transcriptional downregulation of CYCA2s represents a critical mechanism to coordinate proliferation during plant development.}, author = {Vanneste, Steffen and Coppens, Frederik and Lee, EunKyoung and Donner, Tyler J and Xie, Zidian and Van Isterdael, Gert and Dhondt, Stijn and De Winter, Freya and De Rybel, Bert and Vuylsteke, Marnik and De Veylder, Lieven and Jirí Friml and Inzé, Dirk and Grotewold, Erich and Scarpella, Enrico and Sack, Fred and Beemster, Gerrit T and Beeckman, Tom}, journal = {EMBO Journal}, number = {16}, pages = {3430 -- 3441}, publisher = {Wiley-Blackwell}, title = {{Developmental regulation of CYCA2s contributes to tissue-specific proliferation in Arabidopsis }}, doi = {10.1038/emboj.2011.240}, volume = {30}, year = {2011}, } @article{3101, abstract = {Subcellular trafficking is required for a multitude of functions in eukaryotic cells. It involves regulation of cargo sorting, vesicle formation, trafficking and fusion processes at multiple levels. Adaptor protein (AP) complexes are key regulators of cargo sorting into vesicles in yeast and mammals but their existence and function in plants have not been demonstrated. Here we report the identification of the protein-affected trafficking 4 (pat4) mutant defective in the putative δ subunit of the AP-3 complex. pat4 and pat2, a mutant isolated from the same GFP imaging-based forward genetic screen that lacks a functional putative AP-3 β, as well as dominant negative AP-3 μ transgenic lines display undistinguishable phenotypes characterized by largely normal morphology and development, but strong intracellular accumulation of membrane proteins in aberrant vacuolar structures. All mutants are defective in morphology and function of lytic and protein storage vacuoles (PSVs) but show normal sorting of reserve proteins to PSVs. Immunoprecipitation experiments and genetic studies revealed tight functional and physical associations of putative AP-3 β and AP-3 δ subunits. Furthermore, both proteins are closely linked with putative AP-3 μ and σ subunits and several components of the clathrin and dynamin machineries. Taken together, these results demonstrate that AP complexes, similar to those in other eukaryotes, exist in plants, and that AP-3 plays a specific role in the regulation of biogenesis and function of vacuoles in plant cells. © 2011 IBCB, SIBS, CAS All rights reserved}, author = {Zwiewka, Marta and Feraru, Elena and Möller, Barbara and Hwang, Inhwan and Feraru, Mugurel I and Kleine-Vehn, Jürgen and Weijers, Dolf and Jirí Friml}, journal = {Cell Research}, number = {12}, pages = {1711 -- 1722}, publisher = {Nature Publishing Group}, title = {{The AP 3 adaptor complex is required for vacuolar function in Arabidopsis}}, doi = {10.1038/cr.2011.99}, volume = {21}, year = {2011}, } @article{3102, abstract = {Multicellular organisms depend on cell production, cell fate specification, and correct patterning to shape their adult body. In plants, auxin plays a prominent role in the timely coordination of these different cellular processes. A well-studied example is lateral root initiation, in which auxin triggers founder cell specification and cell cycle activation of xylem pole–positioned pericycle cells. Here, we report that the E2Fa transcription factor of Arabidopsis thaliana is an essential component that regulates the asymmetric cell division marking lateral root initiation. Moreover, we demonstrate that E2Fa expression is regulated by the LATERAL ORGAN BOUNDARY DOMAIN18/LATERAL ORGAN BOUNDARY DOMAIN33 (LBD18/LBD33) dimer that is, in turn, regulated by the auxin signaling pathway. LBD18/LBD33 mediates lateral root organogenesis through E2Fa transcriptional activation, whereas E2Fa expression under control of the LBD18 promoter eliminates the need for LBD18. Besides lateral root initiation, vascular patterning is disrupted in E2Fa knockout plants, similarly as it is affected in auxin signaling and lbd mutants, indicating that the transcriptional induction of E2Fa through LBDs represents a general mechanism for auxin-dependent cell cycle activation. Our data illustrate how a conserved mechanism driving cell cycle entry has been adapted evolutionarily to connect auxin signaling with control of processes determining plant architecture. }, author = {Berckmans, Barbara and Vassileva, Valya and Schmid, Stephan P and Maes, Sara and Parizot, Boris and Naramoto, Satoshi and Magyar, Zoltan and Lessa Alvim Kamei, Claire and Koncz, Csaba and Bögre, Laszlo and Persiau, Geert and De Jaeger, Geert and Jirí Friml and Simon, Rüdiger and Beeckman, Tom and de Veyldera, Lieven}, journal = {Plant Cell}, number = {10}, pages = {3671 -- 3683}, publisher = {American Society of Plant Biologists}, title = {{Auxin Dependent cell cycle reactivation through transcriptional regulation of arabidopsis E2Fa by lateral organ boundary proteins}}, doi = {10.1105/tpc.111.088377}, volume = {23}, year = {2011}, } @article{3103, abstract = {Endocytosis in plants has an essential role not only for basic cellular functions but also for growth and development, hormonal signaling and communication with the environment including nutrient delivery, toxin avoidance, and pathogen defense. The major endocytic mechanism in plants depends on the coat protein clathrin. It starts by clathrin-coated vesicle formation at the plasma membrane, where specific cargoes are recognized and packaged for internalization. Recently, genetic, biochemical and advanced microscopy studies provided initial insights into mechanisms and roles of clathrin-mediated endocytosis in plants. Here we summarize the present state of knowledge and compare mechanisms of clathrin-mediated endocytosis in plants with animal and yeast paradigms as well as review plant-specific regulations and roles of this process.}, author = {Chen, Xu and Irani, Niloufer and Friml, Jirí}, journal = {Current Opinion in Plant Biology}, number = {6}, pages = {674 -- 682}, publisher = {Elsevier}, title = {{Clathrin-mediated endocytosis: The gateway into plant cells}}, doi = {10.1016/j.pbi.2011.08.006}, volume = {14}, year = {2011}, } @article{3138, abstract = {Hippocampal sharp waves (SPWs) and associated fast ("ripple") oscillations (SPW-Rs) in the CA1 region are among the most synchronous physiological patterns in the mammalian brain. Using two-dimensional arrays of electrodes for recording local field potentials and unit discharges in freely moving rats, we studied the emergence of ripple oscillations (140-220 Hz) and compared their origin and cellular-synaptic mechanisms with fast gamma oscillations (90-140 Hz). We show that (1) hippocampal SPW-Rs and fast gamma oscillations are quantitatively distinct patterns but involve the same networks and share similar mechanisms; (2) both the frequency and magnitude of fast oscillations are positively correlated with the magnitude of SPWs; (3) during both ripples and fast gamma oscillations the frequency of network oscillation is higher in CA1 than in CA3; and (4) the emergence of CA3 population bursts, a prerequisite for SPW-Rs, is biased by activity patterns in the dentate gyrus and entorhinal cortex, with the highest probability of ripples associated with an "optimum" level of dentate gamma power. We hypothesize that each hippocampal subnetwork possesses distinct resonant properties, tuned by the magnitude of the excitatory drive.}, author = {Sullivan, David W and Jozsef Csicsvari and Mizuseki, Kenji and Montgomery, Sean M and Diba, Kamran and Buzsáki, György}, journal = {Journal of Neuroscience}, number = {23}, pages = {8605 -- 8616}, publisher = {Society for Neuroscience}, title = {{Relationships between hippocampal sharp waves ripples and fast gamma oscillation Influence of dentate and entorhinal cortical activity}}, doi = {10.1523/JNEUROSCI.0294-11.2011}, volume = {31}, year = {2011}, } @article{3145, abstract = {Microinjection of recombinant DNA into zygotic pronuclei has been widely used for producing transgenic mice. However, with this method, the insertion site, integrity, and copy number of the transgene cannot be controlled. Here, we present an integrase-based approach to produce transgenic mice via pronuclear injection, whereby an intact single-copy transgene can be inserted into predetermined chromosomal loci with high efficiency (up to 40%), and faithfully transmitted through generations. We show that neighboring transgenic elements and bacterial DNA within the transgene cause profound silencing and expression variability of the transgenic marker. Removal of these undesirable elements leads to global high-level marker expression from transgenes driven by a ubiquitous promoter. We also obtained faithful marker expression from a tissue-specific promoter. The technique presented here will greatly facilitate murine transgenesis and precise structure/function dissection of mammalian gene function and regulation in vivo.}, author = {Tasic, Bosiljka and Simon Hippenmeyer and Wang, Charlene and Gamboa, Matthew and Zong, Hui and Chen-Tsai, Yanru and Luo, Liqun}, journal = {PNAS}, number = {19}, pages = {7902 -- 7907}, publisher = {National Academy of Sciences}, title = {{Site specific integrase mediated transgenesis in mice via pronuclear injection}}, doi = {10.1073/pnas.1019507108}, volume = {108}, year = {2011}, } @article{3147, abstract = {Cancer cell of origin is difficult to identify by analyzing cells within terminal stage tumors, whose identity could be concealed by the acquired plasticity. Thus, an ideal approach to identify the cell of origin is to analyze proliferative abnormalities in distinct lineages prior to malignancy. Here, we use mosaic analysis with double markers (MADM) in mice to model gliomagenesis by initiating concurrent p53/Nf1 mutations sporadically in neural stem cells (NSCs). Surprisingly, MADM-based lineage tracing revealed significant aberrant growth prior to malignancy only in oligodendrocyte precursor cells (OPCs), but not in any other NSC-derived lineages or NSCs themselves. Upon tumor formation, phenotypic and transcriptome analyses of tumor cells revealed salient OPC features. Finally, introducing the same p53/Nf1 mutations directly into OPCs consistently led to gliomagenesis. Our findings suggest OPCs as the cell of origin in this model, even when initial mutations occur in NSCs, and highlight the importance of analyzing premalignant stages to identify the cancer cell of origin.}, author = {Liu, Chong and Sage, Jonathan C and Miller, Michael R and Verhaak, Roel G and Simon Hippenmeyer and Vogel, Hannes and Foreman, Oded and Bronson, Roderick T and Nishiyama, Akiko and Luo, Liqun and Zong, Hui}, journal = {Cell}, number = {2}, pages = {209 -- 221}, publisher = {Cell Press}, title = {{Mosaic analysis with double markers reveals tumor cell of origin in glioma}}, doi = {10.1016/j.cell.2011.06.014}, volume = {146}, year = {2011}, } @article{3154, abstract = {Regulated adhesion between cells and their environment is critical for normal cell migration. We have identified mutations in a gene encoding the Drosophila hydrogen peroxide (H2O2)-degrading enzyme Jafrac1, which lead to germ cell adhesion defects. During gastrulation, primordial germ cells (PGCs) associate tightly with the invaginating midgut primordium as it enters the embryo; however, in embryos from jafrac1 mutant mothers this association is disrupted, leaving some PGCs trailing on the outside of the embryo. We observed similar phenotypes in embryos from DE-cadherin/shotgun (shg) mutant mothers and were able to rescue the jafrac1 phenotype by increasing DE-cadherin levels. This and our biochemical evidence strongly suggest that Jafrac1-mediated reduction of H2O2 is required to maintain DE-cadherin protein levels in the early embryo. Our results present in vivo evidence of a peroxiredoxin regulating DE-cadherin-mediated adhesion.}, author = {DeGennaro, Matthew and Hurd, Thomas R and Daria Siekhaus and Biteau, Benoit and Jasper, Heinrich and Lehmann, Ruth}, journal = {Developmental Cell}, number = {2}, pages = {233 -- 243}, publisher = {Cell Press}, title = {{Peroxiredoxin stabilization of DE-cadherin promotes primordial germ cell adhesion}}, doi = {10.1016/j.devcel.2010.12.007}, volume = {20}, year = {2011}, } @inproceedings{3163, abstract = {We study multi-label prediction for structured output sets, a problem that occurs, for example, in object detection in images, secondary structure prediction in computational biology, and graph matching with symmetries. Conventional multilabel classification techniques are typically not applicable in this situation, because they require explicit enumeration of the label set, which is infeasible in case of structured outputs. Relying on techniques originally designed for single-label structured prediction, in particular structured support vector machines, results in reduced prediction accuracy, or leads to infeasible optimization problems. In this work we derive a maximum-margin training formulation for multi-label structured prediction that remains computationally tractable while achieving high prediction accuracy. It also shares most beneficial properties with single-label maximum-margin approaches, in particular formulation as a convex optimization problem, efficient working set training, and PAC-Bayesian generalization bounds.}, author = {Lampert, Christoph}, location = {Granada, Spain}, publisher = {Neural Information Processing Systems Foundation}, title = {{Maximum margin multi-label structured prediction}}, year = {2011}, } @inproceedings{3204, abstract = {We introduce a new class of functions that can be minimized in polynomial time in the value oracle model. These are functions f satisfying f(x) + f(y) ≥ f(x ∏ y) + f(x ∐ y) where the domain of each variable x i corresponds to nodes of a rooted binary tree, and operations ∏,∐ are defined with respect to this tree. Special cases include previously studied L-convex and bisubmodular functions, which can be obtained with particular choices of trees. We present a polynomial-time algorithm for minimizing functions in the new class. It combines Murota's steepest descent algorithm for L-convex functions with bisubmodular minimization algorithms. }, author = {Vladimir Kolmogorov}, pages = {400 -- 411}, publisher = {Springer}, title = {{Submodularity on a tree: Unifying Submodularity on a tree: Unifying L-convex and bisubmodular functions convex and bisubmodular functions}}, doi = {10.1007/978-3-642-22993-0_37}, volume = {6907}, year = {2011}, }