@article{9153, abstract = {Internal tide driven mixing plays a key role in sustaining the deep ocean stratification and meridional overturning circulation. Internal tides can be generated by topographic horizontal scales ranging from hundreds of meters to tens of kilometers. State of the art topographic products barely resolve scales smaller than ∼10 km in the deep ocean. On these scales abyssal hills dominate ocean floor roughness. The impact of abyssal hill roughness on internal‐tide generation is evaluated in this study. The conversion of M2 barotropic to baroclinic tidal energy is calculated based on linear wave theory both in real and spectral space using the Shuttle Radar Topography Mission SRTM30_PLUS bathymetric product at 1/120° resolution with and without the addition of synthetic abyssal hill roughness. Internal tide generation by abyssal hills integrates to 0.1 TW globally or 0.03 TW when the energy flux is empirically corrected for supercritical slope (i.e., ∼10% of the energy flux due to larger topographic scales resolved in standard products in both cases). The abyssal hill driven energy conversion is dominated by mid‐ocean ridges, where abyssal hill roughness is large. Focusing on two regions located over the Mid‐Atlantic Ridge and the East Pacific Rise, it is shown that regionally linear theory predicts an increase of the energy flux due to abyssal hills of up to 100% or 60% when an empirical correction for supercritical slopes is attempted. Therefore, abyssal hills, unresolved in state of the art topographic products, can have a strong impact on internal tide generation, especially over mid‐ocean ridges.}, author = {Melet, Angélique and Nikurashin, Maxim and Muller, Caroline J and Falahat, S. and Nycander, Jonas and Timko, Patrick G. and Arbic, Brian K. and Goff, John A.}, issn = {2169-9275}, journal = {Journal of Geophysical Research: Oceans}, number = {11}, pages = {6303--6318}, publisher = {American Geophysical Union}, title = {{Internal tide generation by abyssal hills using analytical theory}}, doi = {10.1002/2013jc009212}, volume = {118}, year = {2013}, } @article{9154, abstract = {In this study the response of tropical precipitation extremes to warming in organized convection is examined using a cloud-resolving model. Vertical shear is imposed to organize the convection into squall lines. Earlier studies show that in disorganized convection, the fractional increase of precipitation extremes is similar to that of surface water vapor, which is substantially smaller than the increase in column water vapor. It has been suggested that organized convection could lead to stronger amplifications. Regardless of the strength of the shear, amplifications of precipitation extremes in the cloud-resolving simulations are comparable to those of surface water vapor and are substantially less than increases in column water vapor. The results without shear and with critical shear, for which the squall lines are perpendicular to the shear, are surprisingly similar with a fractional rate of increase of precipitation extremes slightly smaller than that of surface water vapor. Interestingly, the dependence on shear is nonmonotonic, and stronger supercritical shear yields larger rates, close to or slightly larger than surface humidity. A scaling is used to evaluate the thermodynamic and dynamic contributions to precipitation extreme changes. To first order, they are dominated by the thermodynamic component, which has the same magnitude for all shears, close to the change in surface water vapor. The dynamic contribution plays a secondary role and tends to weaken extremes without shear and with critical shear, while it strengthens extremes with supercritical shear. These different dynamic contributions for different shears are due to different responses of convective mass fluxes in individual updrafts to warming.}, author = {Muller, Caroline J}, issn = {0894-8755}, journal = {Journal of Climate}, keywords = {Atmospheric Science}, number = {14}, pages = {5028--5043}, publisher = {American Meteorological Society}, title = {{Impact of convective organization on the response of tropical precipitation extremes to warming}}, doi = {10.1175/jcli-d-12-00655.1}, volume = {26}, year = {2013}, } @article{9167, abstract = {We introduce a self-propelled colloidal hematite docker that can be steered to a small particle cargo many times its size, dock, transport the cargo to a remote location, and then release it. The self-propulsion and docking are reversible and activated by visible light. The docker can be steered either by a weak uniform magnetic field or by nanoscale tracks in a textured substrate. The light-activated motion and docking originate from osmotic/phoretic particle transport in a concentration gradient of fuel, hydrogen peroxide, induced by the photocatalytic activity of the hematite. The docking mechanism is versatile and can be applied to various materials and shapes. The hematite dockers are simple single-component particles and are synthesized in bulk quantities. This system opens up new possibilities for designing complex micrometer-size factories as well as new biomimetic systems.}, author = {Palacci, Jérémie A and Sacanna, Stefano and Vatchinsky, Adrian and Chaikin, Paul M. and Pine, David J.}, issn = {15205126}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {43}, pages = {15978--15981}, publisher = {American Chemical Society}, title = {{Photoactivated colloidal dockers for cargo transportation}}, doi = {10.1021/ja406090s}, volume = {135}, year = {2013}, } @article{921, abstract = {Recent experiments have shown that spreading epithelial sheets exhibit a long-range coordination of motility forces that leads to a buildup of tension in the tissue, which may enhance cell division and the speed of wound healing. Furthermore, the edges of these epithelial sheets commonly show finger-like protrusions whereas the bulk often displays spontaneous swirls of motile cells. To explain these experimental observations, we propose a simple flocking-type mechanism, in which cells tend to align their motility forceswith their velocity. Implementing this idea in amechanical tissue simulation, the proposed model gives rise to efficient spreading and can explain the experimentally observed long-range alignment of motility forces in highly disordered patterns, as well as the buildup of tensile stress throughout the tissue. Our model also qualitatively reproduces the dependence of swirl size and swirl velocity on cell density reported in experiments and exhibits an undulation instability at the edge of the spreading tissue commonly observed in vivo. Finally, we study the dependence of colony spreading speed on important physical and biological parameters and derive simple scaling relations that show that coordination of motility forces leads to an improvement of the wound healing process for realistic tissue parameters.}, author = {Basan, Markus and Elgeti, Jens and Hannezo, Edouard B and Rappel, Wouter and Levine, Herbert}, journal = {PNAS}, number = {7}, pages = {2452 -- 2459}, publisher = {National Academy of Sciences}, title = {{Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing}}, doi = {10.1073/pnas.1219937110}, volume = {110}, year = {2013}, } @article{7306, abstract = {Rechargeable lithium–air (O2) batteries are receiving intense interest because their high theoretical specific energy exceeds that of lithium-ion batteries. If the Li–O2 battery is ever to succeed, highly reversible formation/decomposition of Li2O2 must take place at the cathode on cycling. However, carbon, used ubiquitously as the basis of the cathode, decomposes during Li2O2 oxidation on charge and actively promotes electrolyte decomposition on cycling. Replacing carbon with a nanoporous gold cathode, when in contact with a dimethyl sulphoxide-based electrolyte, does seem to demonstrate better stability. However, nanoporous gold is not a suitable cathode; its high mass destroys the key advantage of Li–O2 over Li ion (specific energy), it is too expensive and too difficult to fabricate. Identifying a suitable cathode material for the Li–O2 cell is one of the greatest challenges at present. Here we show that a TiC-based cathode reduces greatly side reactions (arising from the electrolyte and electrode degradation) compared with carbon and exhibits better reversible formation/decomposition of Li2O2 even than nanoporous gold (>98% capacity retention after 100 cycles, compared with 95% for nanoporous gold); it is also four times lighter, of lower cost and easier to fabricate. The stability may originate from the presence of TiO2 (along with some TiOC) on the surface of TiC. In contrast to carbon or nanoporous gold, TiC seems to represent a more viable, stable, cathode for aprotic Li–O2 cells.}, author = {Ottakam Thotiyl, Muhammed M. and Freunberger, Stefan Alexander and Peng, Zhangquan and Chen, Yuhui and Liu, Zheng and Bruce, Peter G.}, issn = {1476-1122}, journal = {Nature Materials}, number = {11}, pages = {1050--1056}, publisher = {Springer Nature}, title = {{A stable cathode for the aprotic Li–O2 battery}}, doi = {10.1038/nmat3737}, volume = {12}, year = {2013}, } @article{7307, abstract = {The non-aqueous Li–air (O2) battery is receiving intense interest because its theoretical specific energy exceeds that of Li-ion batteries. Recharging the Li–O2 battery depends on oxidizing solid lithium peroxide (Li2O2), which is formed on discharge within the porous cathode. However, transporting charge between Li2O2 particles and the solid electrode surface is at best very difficult and leads to voltage polarization on charging, even at modest rates. This is a significant problem facing the non-aqueous Li–O2 battery. Here we show that incorporation of a redox mediator, tetrathiafulvalene (TTF), enables recharging at rates that are impossible for the cell in the absence of the mediator. On charging, TTF is oxidized to TTF+ at the cathode surface; TTF+ in turn oxidizes the solid Li2O2, which results in the regeneration of TTF. The mediator acts as an electron–hole transfer agent that permits efficient oxidation of solid Li2O2. The cell with the mediator demonstrated 100 charge/discharge cycles.}, author = {Chen, Yuhui and Freunberger, Stefan Alexander and Peng, Zhangquan and Fontaine, Olivier and Bruce, Peter G.}, issn = {1755-4330}, journal = {Nature Chemistry}, number = {6}, pages = {489--494}, publisher = {Springer Nature}, title = {{Charging a Li–O2 battery using a redox mediator}}, doi = {10.1038/nchem.1646}, volume = {5}, year = {2013}, } @article{7595, abstract = {Inositol 1,3,4-trisphosphate 5/6 kinase (ITPK) phosphorylates inositol 1,3,4-trisphosphate to form inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4,6-tetrakisphosphate which can be finally transferred to inositol hexaphosphate (IP6) and play important roles during plant growth and development. There are 4 putative ITPK members in Arabidopsis. Expression pattern analysis showed that ITPK2 is constitutively expressed in various tissues. A T-DNA knockout mutant of ITPK2 was identified and scanning electron microscopy (SEM) analysis showed that the epidermis structure of seed coat was irregularly formed in seeds of itpk2-1 mutant, resulting in the increased permeability of seed coat to tetrazolium salts. Further analysis by gas chromatography coupled with mass spectrometry of lipid polyester monomers in cell wall confirmed a dramatic decrease in composition of suberin and cutin, which relate to the permeability of seed coat and the formation of which is accompanied with seed coat development. These results indicate that ITPK2 plays an essential role in seed coat development and lipid polyester barrier formation.}, author = {Tang, Yong and Tan, Shutang and Xue, Hongwei}, issn = {1745-7270}, journal = {Acta Biochimica et Biophysica Sinica}, number = {7}, pages = {549--560}, publisher = {Oxford University Press}, title = {{Arabidopsis inositol 1,3,4-trisphosphate 5/6 kinase 2 is required for seed coat development}}, doi = {10.1093/abbs/gmt039}, volume = {45}, year = {2013}, } @article{7596, abstract = {Casein kinase1 (CK1) plays crucial roles in regulating growth and development via phosphorylating various substrates throughout the eukaryote kingdom. Blue light is crucial for normal growth of both plants and animals, and blue light receptor cryptochrome2 (CRY2) undergoes blue light–dependent phosphorylation and degradation in planta. To study the function of plant CK1s, systematic genetic analysis showed that deficiency of two paralogous Arabidopsis thaliana CK1s, CK1.3 and CK1.4, caused shortened hypocotyls, especially under blue light, while overexpression of either CK1.3 or CK1.4 resulted in the insensitive response to blue light and delayed flowering under long-day conditions. CK1.3 or CK1.4 act dependently on CRY2, and overexpression of CK1.3 or CK1.4 significantly suppresses the hypersensitive response to blue light by CRY2 overexpression. Biochemical studies showed that CK1.3 and CK1.4 directly phosphorylate CRY2 at Ser-587 and Thr-603 in vitro and negatively regulate CRY2 stability in planta, which are stimulated by blue light, further confirming the crucial roles of CK1.3 and CK1.4 in blue light responses through phosphorylating CRY2. Interestingly, expression of CK1.3 and CK1.4 is stimulated by blue light and feedback regulated by CRY2-mediated signaling. These results provide direct evidence for CRY2 phosphorylation and informative clues on the mechanisms of CRY2-mediated light responses.}, author = {Tan, Shutang and Dai, C. and Liu, H.-T. and Xue, H.-W.}, issn = {1040-4651}, journal = {The Plant Cell}, number = {7}, pages = {2618--2632}, publisher = {American Society of Plant Biologists}, title = {{Arabidopsis casein kinase1 proteins CK1.3 and CK1.4 phosphorylate cryptochrome2 to regulate blue light signaling}}, doi = {10.1105/tpc.113.114322}, volume = {25}, year = {2013}, } @inproceedings{765, abstract = {Renaming is a classic distributed coordination task in which a set of processes must pick distinct identifiers from a small namespace. In this paper, we consider the time complexity of this problem when the namespace is linear in the number of participants, a variant known as loose renaming. We give a non-adaptive algorithm with O(log log n) (individual) step complexity, where n is a known upper bound on contention, and an adaptive algorithm with step complexity O((log log k)2), where k is the actual contention in the execution. We also present a variant of the adaptive algorithm which requires O(k log log k) total process steps. All upper bounds hold with high probability against a strong adaptive adversary. We complement the algorithms with an ω(log log n) expected time lower bound on the complexity of randomized renaming using test-and-set operations and linear space. The result is based on a new coupling technique, and is the first to apply to non-adaptive randomized renaming. Since our algorithms use O(n) test-and-set objects, our results provide matching bounds on the cost of loose renaming in this setting.}, author = {Alistarh, Dan-Adrian and Aspnes, James and Giakkoupis, George and Woelfel, Philipp}, pages = {200 -- 209}, publisher = {ACM}, title = {{Randomized loose renaming in O(loglogn) time}}, doi = {10.1145/2484239.2484240}, year = {2013}, } @article{7745, abstract = {The underlying basis of genetic variation in quantitative traits, in terms of the number of causal variants and the size of their effects, is largely unknown in natural populations. The expectation is that complex quantitative trait variation is attributable to many, possibly interacting, causal variants, whose effects may depend upon the sex, age and the environment in which they are expressed. A recently developed methodology in animal breeding derives a value of relatedness among individuals from high‐density genomic marker data, to estimate additive genetic variance within livestock populations. Here, we adapt and test the effectiveness of these methods to partition genetic variation for complex traits across genomic regions within ecological study populations where individuals have varying degrees of relatedness. We then apply this approach for the first time to a natural population and demonstrate that genetic variation in wing length in the great tit (Parus major) reflects contributions from multiple genomic regions. We show that a polygenic additive mode of gene action best describes the patterns observed, and we find no evidence of dosage compensation for the sex chromosome. Our results suggest that most of the genomic regions that influence wing length have the same effects in both sexes. We found a limited amount of genetic variance in males that is attributed to regions that have no effects in females, which could facilitate the sexual dimorphism observed for this trait. Although this exploratory work focuses on one complex trait, the methodology is generally applicable to any trait for any laboratory or wild population, paving the way for investigating sex‐, age‐ and environment‐specific genetic effects and thus the underlying genetic architecture of phenotype in biological study systems.}, author = {Robinson, Matthew Richard and Santure, Anna W. and DeCauwer, Isabelle and Sheldon, Ben C. and Slate, Jon}, issn = {0962-1083}, journal = {Molecular Ecology}, number = {15}, pages = {3963--3980}, publisher = {Wiley}, title = {{Partitioning of genetic variation across the genome using multimarker methods in a wild bird population}}, doi = {10.1111/mec.12375}, volume = {22}, year = {2013}, } @article{7746, abstract = {Clutch size and egg mass are life history traits that have been extensively studied in wild bird populations, as life history theory predicts a negative trade‐off between them, either at the phenotypic or at the genetic level. Here, we analyse the genomic architecture of these heritable traits in a wild great tit (Parus major) population, using three marker‐based approaches – chromosome partitioning, quantitative trait locus (QTL) mapping and a genome‐wide association study (GWAS). The variance explained by each great tit chromosome scales with predicted chromosome size, no location in the genome contains genome‐wide significant QTL, and no individual SNPs are associated with a large proportion of phenotypic variation, all of which may suggest that variation in both traits is due to many loci of small effect, located across the genome. There is no evidence that any regions of the genome contribute significantly to both traits, which combined with a small, nonsignificant negative genetic covariance between the traits, suggests the absence of genetic constraints on the independent evolution of these traits. Our findings support the hypothesis that variation in life history traits in natural populations is likely to be determined by many loci of small effect spread throughout the genome, which are subject to continued input of variation by mutation and migration, although we cannot exclude the possibility of an additional input of major effect genes influencing either trait.}, author = {Santure, Anna W. and De Cauwer, Isabelle and Robinson, Matthew Richard and Poissant, Jocelyn and Sheldon, Ben C. and Slate, Jon}, issn = {0962-1083}, journal = {Molecular Ecology}, number = {15}, pages = {3949--3962}, publisher = {Wiley}, title = {{Genomic dissection of variation in clutch size and egg mass in a wild great tit (Parus major) population}}, doi = {10.1111/mec.12376}, volume = {22}, year = {2013}, } @article{7747, abstract = {Acquisition and allocation of resources are central to life‐history theory. However, empirical work typically focuses only on allocation despite the fact that relationships between fitness components may be governed by differences in the ability of individuals to acquire resources across environments. Here, we outline a statistical framework to partition the genetic basis of multivariate plasticity into independent axes of genetic variation, and quantify for the first time, the extent to which specific traits drive multitrait genotype–environment interactions. Our framework generalises to analyses of plasticity, growth and ageing. We apply this approach to a unique, large‐scale, multivariate study of acquisition, allocation and plasticity in the life history of the cricket, Gryllus firmus. We demonstrate that resource acquisition and allocation are genetically correlated, and that plasticity in trade‐offs between allocation to components of fitness is 90% dependent on genetic variance for total resource acquisition. These results suggest that genotype–environment effects for resource acquisition can maintain variation in life‐history components that are typically observed in the wild.}, author = {Robinson, Matthew Richard and Beckerman, Andrew P.}, issn = {1461-023X}, journal = {Ecology Letters}, number = {3}, pages = {281--290}, publisher = {Wiley}, title = {{Quantifying multivariate plasticity: Genetic variation in resource acquisition drives plasticity in resource allocation to components of life history}}, doi = {10.1111/ele.12047}, volume = {16}, year = {2013}, } @article{7774, abstract = {In 2005, Wyart et al. [Europhys. Lett., 2005, 72, 486] showed that the low frequency vibrational properties of jammed amorphous sphere packings can be understood in terms of a length scale, called l*, that diverges as the system becomes marginally unstable. Despite the tremendous success of this theory, it has been difficult to connect the counting argument that defines l* to other length scales that diverge near the jamming transition. We present an alternate derivation of l* based on the onset of rigidity. This phenomenological approach reveals the physical mechanism underlying the length scale and is relevant to a range of systems for which the original argument breaks down. It also allows us to present the first direct numerical measurement of l*.}, author = {Goodrich, Carl Peter and Ellenbroek, Wouter G. and Liu, Andrea J.}, issn = {1744-683X}, journal = {Soft Matter}, number = {46}, publisher = {Royal Society of Chemistry}, title = {{Stability of jammed packings I: The rigidity length scale}}, doi = {10.1039/c3sm51095f}, volume = {9}, year = {2013}, } @article{7775, abstract = {As a function of packing fraction at zero temperature and applied stress, an amorphous packing of spheres exhibits a jamming transition where the system is sensitive to boundary conditions even in the thermodynamic limit. Upon further compression, the system should become insensitive to boundary conditions provided it is sufficiently large. Here we explore the linear response to a large class of boundary perturbations in 2 and 3 dimensions. We consider each finite packing with periodic-boundary conditions as the basis of an infinite square or cubic lattice and study properties of vibrational modes at arbitrary wave vector. We find that the stability of such modes can be understood in terms of a competition between plane waves and the anomalous vibrational modes associated with the jamming transition; infinitesimal boundary perturbations become irrelevant for systems that are larger than a length scale that characterizes the transverse excitations. This previously identified length diverges at the jamming transition.}, author = {Schoenholz, Samuel S. and Goodrich, Carl Peter and Kogan, Oleg and Liu, Andrea J. and Nagel, Sidney R.}, issn = {1744-683X}, journal = {Soft Matter}, number = {46}, publisher = {Royal Society of Chemistry}, title = {{Stability of jammed packings II: The transverse length scale}}, doi = {10.1039/c3sm51096d}, volume = {9}, year = {2013}, } @article{7785, abstract = {Neural circuit assembly requires selection of specific cell fates, axonal trajectories, and synaptic targets. By analyzing the function of a secreted semaphorin, Sema-2b, in Drosophila olfactory receptor neuron (ORN) development, we identified multiple molecular and cellular mechanisms that link these events. Notch signaling limits Sema-2b expression to ventromedial ORN classes, within which Sema-2b cell-autonomously sensitizes ORN axons to external semaphorins. Central-brain-derived Sema-2a and Sema-2b attract Sema-2b-expressing axons to the ventromedial trajectory. In addition, Sema-2b/PlexB-mediated axon-axon interactions consolidate this trajectory choice and promote ventromedial axon-bundle formation. Selecting the correct developmental trajectory is ultimately essential for proper target choice. These findings demonstrate that Sema-2b couples ORN axon guidance to postsynaptic target neuron dendrite patterning well before the final target selection phase, and exemplify how a single guidance molecule can drive consecutive stages of neural circuit assembly with the help of sophisticated spatial and temporal regulation.}, author = {Joo, William J. and Sweeney, Lora Beatrice Jaeger and Liang, Liang and Luo, Liqun}, issn = {0896-6273}, journal = {Neuron}, number = {4}, pages = {673--686}, publisher = {Elsevier}, title = {{Linking cell fate, trajectory choice, and target selection: Genetic analysis of sema-2b in olfactory axon targeting}}, doi = {10.1016/j.neuron.2013.03.022}, volume = {78}, year = {2013}, } @article{8030, abstract = {While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.}, author = {Vogels, Tim P and Froemke, R. C. and Doyon, N. and Gilson, M. and Haas, J. S. and Liu, R. and Maffei, A. and Miller, P. and Wierenga, C. J. and Woodin, M. A. and Zenke, F. and Sprekeler, H.}, issn = {1662-5110}, journal = {Frontiers in Neural Circuits}, publisher = {Frontiers Media}, title = {{Inhibitory synaptic plasticity: Spike timing-dependence and putative network function}}, doi = {10.3389/fncir.2013.00119}, volume = {7}, year = {2013}, } @article{810, abstract = {Cryo-electron tomography combined with image processing by sub-tomogram averaging is unique in its power to resolve the structures of proteins and macromolecular complexes in situ. Limitations of the method, including the low signal to noise ratio within individual images from cryo-tomographic datasets and difficulties in determining the defocus at which the data was collected, mean that to date the very best structures obtained by sub-tomogram averaging are limited to a resolution of approximately 15. Å. Here, by optimizing data collection and defocus determination steps, we have determined the structure of assembled Mason-Pfizer monkey virus Gag protein using sub-tomogram averaging to a resolution of 8.5. Å. At this resolution alpha-helices can be directly and clearly visualized. These data demonstrate for the first time that high-resolution structural information can be obtained from cryo-electron tomograms using sub-tomogram averaging. Sub-tomogram averaging has the potential to allow detailed studies of unsolved and biologically relevant structures under biologically relevant conditions.}, author = {Florian Schur and Hagen, Wim J and De Marco, Alex and Briggs, John A}, journal = {Journal of Structural Biology}, number = {3}, pages = {394 -- 400}, publisher = {Academic Press}, title = {{Determination of protein structure at 8.5Å resolution using cryo-electron tomography and sub-tomogram averaging}}, doi = {10.1016/j.jsb.2013.10.015}, volume = {184}, year = {2013}, } @article{811, abstract = {Cell migration is commonly accompanied by protrusion of membrane ruffles and lamellipodia. In two-dimensional migration, protrusion of these thin sheets of cytoplasm is considered relevant to both exploration of new space and initiation of nascent adhesion to the substratum. Lamellipodium formation can be potently stimulated by Rho GTPases of the Rac subfamily, but alsoby RhoG or Cdc42. Here we describe viable fibroblast cell lines geneticallydeficient for Rac1 that lack detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent lamellipodia, but these structures were restored by expression of either Rac subfamily member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction in wound closure and random cell migration and a notable loss of sensitivity to a chemotactic gradient. Despite these defects, Rac-deficient cells were able to spread, formed filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were largely unaffected by genetic removal of Rac1. However, Rac deficiency increased the mobility of different components in focal adhesions, potentially explaining how Rac - although not essential - can contribute to focal adhesion assembly. Together, our data demonstrate that Rac signaling is essential for lamellipodium protrusion and for efficient cell migration, but not for spreading or filopodium formation. Our findings also suggest that Rac GTPases are crucial to the establishment or maintenance of polarity in chemotactic migration.}, author = {Steffen, Anika and Ladwein, Markus and Georgi Dimchev and Hein, Anke and Schwenkmezger, Lisa and Arens, Stefan and Ladwein, Kathrin I and Holleboom, J. Margit and Florian Schur and Small, John V and Schwarz, Janett and Gerhard, Ralf and Faix, Jan and Stradal, Theresia E and Brakebusch, Cord H and Rottner, Klemens}, journal = {Journal of Cell Science}, number = {20}, pages = {4572 -- 4588}, publisher = {Company of Biologists}, title = {{Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation}}, doi = {10.1242/jcs.118232}, volume = {126}, year = {2013}, } @article{812, abstract = {Lamellipodia are sheet-like protrusions formed during migration or phagocytosis and comprise a network of actin filaments. Filament formation in this network is initiated by nucleation/branching through the actin-related protein 2/3 (Arp2/3) complex downstream of its activator, suppressor of cAMP receptor/WASP-family verprolin homologous (Scar/WAVE), but the relative relevance of Arp2/3-mediated branching versus actin filament elongation is unknown. Here we use instantaneous interference with Arp2/3 complex function in live fibroblasts with established lamellipodia. This allows direct examination of both the fate of elongating filaments upon instantaneous suppression of Arp2/3 complex activity and the consequences of this treatment on the dynamics of other lamellipodial regulators. We show that Arp2/3 complex is an essential organizer of treadmilling actin filament arrays but has little effect on the net rate of actin filament turnover at the cell periphery. In addition, Arp2/3 complex serves as key upstream factor for the recruitment of modulators of lamellipodia formation such as capping protein or cofilin. Arp2/3 complex is thus decisive for filament organization and geometry within the network not only by generating branches and novel filament ends, but also by directing capping or severing activities to the lamellipodium. Arp2/3 complex is also crucial to lamellipodia-based migration of keratocytes.}, author = {Koestler, Stefan A and Steffen, Anika and Maria Nemethova and Winterhoff, Moritz and Luo, Ningning and Holleboom, J. Margit and Krupp, Jessica and Jacob, Sonja and Vinzenz, Marlene and Florian Schur and Schlüter, Kai and Gunning, Peter W and Winkler, Christoph and Schmeiser, Christian and Faix, Jan and Stradal, Theresia E and Small, John V and Rottner, Klemens}, journal = {Molecular Biology of the Cell}, number = {18}, pages = {2861 -- 2875}, publisher = {American Society for Biology}, title = {{Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin}}, doi = {10.1091/mbc.E12-12-0857}, volume = {24}, year = {2013}, } @article{1726, abstract = {The development of a functional tissue requires coordination of the amplification of progenitors and their differentiation into specific cell types. The molecular basis for this coordination during myotome ontogeny is not well understood. Dermomytome progenitors that colonize the myotome first acquire myocyte identity and subsequently proliferate as Pax7-expressing progenitors before undergoing terminal differentiation. We show that the dynamics of sonic hedgehog (Shh) signaling is crucial for this transition in both avian and mouse embryos. Initially, Shh ligand emanating from notochord/floor plate reaches the dermomyotome, where it both maintains the proliferation of dermomyotome cells and promotes myogenic differentiation of progenitors that colonized the myotome. Interfering with Shh signaling at this stage produces small myotomes and accumulation of Pax7-expressing progenitors. An in vivo reporter of Shh activity combined with mouse genetics revealed the existence of both activator and repressor Shh activities operating on distinct subsets of cells during the epaxial myotomal maturation. In contrast to observations in mice, in avians Shh promotes the differentiation of both epaxial and hypaxial myotome domains. Subsequently, myogenic progenitors become refractory to Shh; this is likely to occur at the level of, or upstream of, smoothened signaling. The end of responsiveness to Shh coincides with, and is thus likely to enable, the transition into the growth phase of the myotome.}, author = {Kahane, Nitza and Ribes, Vanessa and Anna Kicheva and Briscoe, James and Kalcheim, Chaya}, journal = {Development}, number = {8}, pages = {1740 -- 1750}, publisher = {Company of Biologists}, title = {{The transition from differentiation to growth during dermomyotome-derived myogenesis depends on temporally restricted hedgehog signaling}}, doi = {10.1242/dev.092726}, volume = {140}, year = {2013}, }