@article{726, abstract = {The morphogenesis of branched organs remains a subject of abiding interest. Although much is known about the underlying signaling pathways, it remains unclear how macroscopic features of branched organs, including their size, network topology, and spatial patterning, are encoded. Here, we show that, in mouse mammary gland, kidney, and human prostate, these features can be explained quantitatively within a single unifying framework of branching and annihilating random walks. Based on quantitative analyses of large-scale organ reconstructions and proliferation kinetics measurements, we propose that morphogenesis follows from the proliferative activity of equipotent tips that stochastically branch and randomly explore their environment but compete neutrally for space, becoming proliferatively inactive when in proximity with neighboring ducts. These results show that complex branched epithelial structures develop as a self-organized process, reliant upon a strikingly simple but generic rule, without recourse to a rigid and deterministic sequence of genetically programmed events.}, author = {Hannezo, Edouard B and Scheele, Colinda and Moad, Mohammad and Drogo, Nicholas and Heer, Rakesh and Sampogna, Rosemary and Van Rheenen, Jacco and Simons, Benjamin}, issn = {00928674}, journal = {Cell}, number = {1}, pages = {242 -- 255}, publisher = {Cell Press}, title = {{A unifying theory of branching morphogenesis}}, doi = {10.1016/j.cell.2017.08.026}, volume = {171}, year = {2017}, } @article{727, abstract = {Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. In a steady state, migrating cell filaments assume the canonical dendritic geometry, defined by Arp2/3-generated 70° branch points. Increased tension triggers a dense network with a broadened range of angles, whereas decreased tension causes a shift to a sparse configuration dominated by filaments growing perpendicularly to the plasma membrane. We show that these responses emerge from the geometry of branched actin: when load per filament decreases, elongation speed increases and perpendicular filaments gradually outcompete others because they polymerize the shortest distance to the membrane, where they are protected from capping. This network-intrinsic geometrical adaptation mechanism tunes protrusive force in response to mechanical load.}, author = {Mueller, Jan and Szep, Gregory and Nemethova, Maria and De Vries, Ingrid and Lieber, Arnon and Winkler, Christoph and Kruse, Karsten and Small, John and Schmeiser, Christian and Keren, Kinneret and Hauschild, Robert and Sixt, Michael K}, issn = {00928674}, journal = {Cell}, number = {1}, pages = {188 -- 200}, publisher = {Cell Press}, title = {{Load adaptation of lamellipodial actin networks}}, doi = {10.1016/j.cell.2017.07.051}, volume = {171}, year = {2017}, } @article{728, abstract = {During animal development, cell-fate-specific changes in gene expression can modify the material properties of a tissue and drive tissue morphogenesis. While mechanistic insights into the genetic control of tissue-shaping events are beginning to emerge, how tissue morphogenesis and mechanics can reciprocally impact cell-fate specification remains relatively unexplored. Here we review recent findings reporting how multicellular morphogenetic events and their underlying mechanical forces can feed back into gene regulatory pathways to specify cell fate. We further discuss emerging techniques that allow for the direct measurement and manipulation of mechanical signals in vivo, offering unprecedented access to study mechanotransduction during development. Examination of the mechanical control of cell fate during tissue morphogenesis will pave the way to an integrated understanding of the design principles that underlie robust tissue patterning in embryonic development.}, author = {Chan, Chii and Heisenberg, Carl-Philipp J and Hiiragi, Takashi}, issn = {09609822}, journal = {Current Biology}, number = {18}, pages = {R1024 -- R1035}, publisher = {Cell Press}, title = {{Coordination of morphogenesis and cell fate specification in development}}, doi = {10.1016/j.cub.2017.07.010}, volume = {27}, year = {2017}, } @article{729, abstract = {The cellular mechanisms allowing tissues to efficiently regenerate are not fully understood. In this issue of Developmental Cell, Cao et al. (2017)) discover that during zebrafish heart regeneration, epicardial cells at the leading edge of regenerating tissue undergo endoreplication, possibly due to increased tissue tension, thereby boosting their regenerative capacity.}, author = {Spiro, Zoltan P and Heisenberg, Carl-Philipp J}, issn = {15345807}, journal = {Developmental Cell}, number = {6}, pages = {559 -- 560}, publisher = {Cell Press}, title = {{Regeneration tensed up polyploidy takes the lead}}, doi = {10.1016/j.devcel.2017.09.008}, volume = {42}, year = {2017}, } @article{730, abstract = {Neural responses are highly structured, with population activity restricted to a small subset of the astronomical range of possible activity patterns. Characterizing these statistical regularities is important for understanding circuit computation, but challenging in practice. Here we review recent approaches based on the maximum entropy principle used for quantifying collective behavior in neural activity. We highlight recent models that capture population-level statistics of neural data, yielding insights into the organization of the neural code and its biological substrate. Furthermore, the MaxEnt framework provides a general recipe for constructing surrogate ensembles that preserve aspects of the data, but are otherwise maximally unstructured. This idea can be used to generate a hierarchy of controls against which rigorous statistical tests are possible.}, author = {Savin, Cristina and Tkacik, Gasper}, issn = {09594388}, journal = {Current Opinion in Neurobiology}, pages = {120 -- 126}, publisher = {Elsevier}, title = {{Maximum entropy models as a tool for building precise neural controls}}, doi = {10.1016/j.conb.2017.08.001}, volume = {46}, year = {2017}, } @article{731, abstract = {Genetic variations in the oxytocin receptor gene affect patients with ASD and ADHD differently.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {411}, publisher = {American Association for the Advancement of Science}, title = {{The science of love in ASD and ADHD}}, doi = {10.1126/scitranslmed.aap8168}, volume = {9}, year = {2017}, } @article{732, abstract = {Background: Social insects form densely crowded societies in environments with high pathogen loads, but have evolved collective defences that mitigate the impact of disease. However, colony-founding queens lack this protection and suffer high rates of mortality. The impact of pathogens may be exacerbated in species where queens found colonies together, as healthy individuals may contract pathogens from infectious co-founders. Therefore, we tested whether ant queens avoid founding colonies with pathogen-exposed conspecifics and how they might limit disease transmission from infectious individuals. Results: Using Lasius Niger queens and a naturally infecting fungal pathogen Metarhizium brunneum, we observed that queens were equally likely to found colonies with another pathogen-exposed or sham-treated queen. However, when one queen died, the surviving individual performed biting, burial and removal of the corpse. These undertaking behaviours were performed prophylactically, i.e. targeted equally towards non-infected and infected corpses, as well as carried out before infected corpses became infectious. Biting and burial reduced the risk of the queens contracting and dying from disease from an infectious corpse of a dead co-foundress. Conclusions: We show that co-founding ant queens express undertaking behaviours that, in mature colonies, are performed exclusively by workers. Such infection avoidance behaviours act before the queens can contract the disease and will therefore improve the overall chance of colony founding success in ant queens.}, author = {Pull, Christopher and Cremer, Sylvia}, issn = {14712148}, journal = {BMC Evolutionary Biology}, number = {1}, publisher = {BioMed Central}, title = {{Co-founding ant queens prevent disease by performing prophylactic undertaking behaviour}}, doi = {10.1186/s12862-017-1062-4}, volume = {17}, year = {2017}, } @article{733, abstract = {Let A and B be two N by N deterministic Hermitian matrices and let U be an N by N Haar distributed unitary matrix. It is well known that the spectral distribution of the sum H = A + UBU∗ converges weakly to the free additive convolution of the spectral distributions of A and B, as N tends to infinity. We establish the optimal convergence rate in the bulk of the spectrum.}, author = {Bao, Zhigang and Erdös, László and Schnelli, Kevin}, journal = {Advances in Mathematics}, pages = {251 -- 291}, publisher = {Academic Press}, title = {{Convergence rate for spectral distribution of addition of random matrices}}, doi = {10.1016/j.aim.2017.08.028}, volume = {319}, year = {2017}, } @article{734, abstract = {Social insect societies are long-standing models for understanding social behaviour and evolution. Unlike other advanced biological societies (such as the multicellular body), the component parts of social insect societies can be easily deconstructed and manipulated. Recent methodological and theoretical innovations have exploited this trait to address an expanded range of biological questions. We illustrate the broadening range of biological insight coming from social insect biology with four examples. These new frontiers promote open-minded, interdisciplinary exploration of one of the richest and most complex of biological phenomena: sociality.}, author = {Kennedy, Patrick and Baron, Gemma and Qiu, Bitao and Freitak, Dalial and Helantera, Heikki and Hunt, Edmund and Manfredini, Fabio and O'Shea Wheller, Thomas and Patalano, Solenn and Pull, Christopher and Sasaki, Takao and Taylor, Daisy and Wyatt, Christopher and Sumner, Seirian}, issn = {01695347}, journal = {Trends in Ecology and Evolution}, number = {11}, pages = {861 -- 872}, publisher = {Cell Press}, title = {{Deconstructing superorganisms and societies to address big questions in biology}}, doi = {10.1016/j.tree.2017.08.004}, volume = {32}, year = {2017}, } @article{735, abstract = {Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo.}, author = {Barone, Vanessa and Lang, Moritz and Krens, Gabriel and Pradhan, Saurabh and Shamipour, Shayan and Sako, Keisuke and Sikora, Mateusz K and Guet, Calin C and Heisenberg, Carl-Philipp J}, issn = {15345807}, journal = {Developmental Cell}, number = {2}, pages = {198 -- 211}, publisher = {Cell Press}, title = {{An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate}}, doi = {10.1016/j.devcel.2017.09.014}, volume = {43}, year = {2017}, } @article{736, abstract = {The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.}, author = {Rubio, María and Matsui, Ko and Fukazawa, Yugo and Kamasawa, Naomi and Harada, Harumi and Itakura, Makoto and Molnár, Elek and Abe, Manabu and Sakimura, Kenji and Shigemoto, Ryuichi}, issn = {18632653}, journal = {Brain Structure and Function}, number = {8}, pages = {3375 -- 3393}, publisher = {Springer}, title = {{The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells}}, doi = {10.1007/s00429-017-1408-0}, volume = {222}, year = {2017}, } @article{7360, abstract = {Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a “thresholder” to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device. This genetic circuit was autonomously activated by inflammatory signals, including endogenous cecal ligation and puncture (CLP)-induced inflammation in mice and serum from a systemic juvenile idiopathic arthritis (sIJA) patient, and could be reset externally by a chemical signal. The microencapsulated anti-inflammatory device significantly reduced the pathology in dextran sodium sulfate (DSS)-induced acute murine colitis, demonstrating a synthetic immunological approach for autonomous anti-inflammatory therapy.}, author = {Smole, Anže and Lainšček, Duško and Bezeljak, Urban and Horvat, Simon and Jerala, Roman}, issn = {1525-0016}, journal = {Molecular Therapy}, number = {1}, pages = {102--119}, publisher = {Elsevier}, title = {{A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation}}, doi = {10.1016/j.ymthe.2016.10.005}, volume = {25}, year = {2017}, } @article{737, abstract = {We generalize Brazas’ topology on the fundamental group to the whole universal path space X˜ i.e., to the set of homotopy classes of all based paths. We develop basic properties of the new notion and provide a complete comparison of the obtained topology with the established topologies, in particular with the Lasso topology and the CO topology, i.e., the topology that is induced by the compact-open topology. It turns out that the new topology is the finest topology contained in the CO topology, for which the action of the fundamental group on the universal path space is a continuous group action.}, author = {Virk, Ziga and Zastrow, Andreas}, issn = {01668641}, journal = {Topology and its Applications}, pages = {186 -- 196}, publisher = {Elsevier}, title = {{A new topology on the universal path space}}, doi = {10.1016/j.topol.2017.09.015}, volume = {231}, year = {2017}, } @article{739, abstract = {We study the norm approximation to the Schrödinger dynamics of N bosons in with an interaction potential of the form . Assuming that in the initial state the particles outside of the condensate form a quasi-free state with finite kinetic energy, we show that in the large N limit, the fluctuations around the condensate can be effectively described using Bogoliubov approximation for all . The range of β is expected to be optimal for this large class of initial states.}, author = {Nam, Phan and Napiórkowski, Marcin M}, issn = {00217824}, journal = {Journal de Mathématiques Pures et Appliquées}, number = {5}, pages = {662 -- 688}, publisher = {Elsevier}, title = {{A note on the validity of Bogoliubov correction to mean field dynamics}}, doi = {10.1016/j.matpur.2017.05.013}, volume = {108}, year = {2017}, } @article{740, abstract = {Developments in bioengineering and molecular biology have introduced a palette of genetically encoded probes for identification of specific cell populations in electron microscopy. These probes can be targeted to distinct cellular compartments, rendering them electron dense through a subsequent chemical reaction. These electron densities strongly increase the local contrast in samples prepared for electron microscopy, allowing three major advances in ultrastructural mapping of circuits: genetic identification of circuit components, targeted imaging of regions of interest and automated analysis of the tagged circuits. Together, the gains from these advances can decrease the time required for the analysis of targeted circuit motifs by over two orders of magnitude. These genetic encoded tags for electron microscopy promise to simplify the analysis of circuit motifs and become a central tool for structure‐function studies of synaptic connections in the brain. We review the current state‐of‐the‐art with an emphasis on connectomics, the quantitative analysis of neuronal structures and motifs.}, author = {Shigemoto, Ryuichi and Jösch, Maximilian A}, issn = {17597684}, journal = {WIREs Developmental Biology}, number = {6}, publisher = {Wiley-Blackwell}, title = {{The genetic encoded toolbox for electron microscopy and connectomics}}, doi = {10.1002/wdev.288}, volume = {6}, year = {2017}, } @article{741, abstract = {We prove that a system of N fermions interacting with an additional particle via point interactions is stable if the ratio of the mass of the additional particle to the one of the fermions is larger than some critical m*. The value of m* is independent of N and turns out to be less than 1. This fact has important implications for the stability of the unitary Fermi gas. We also characterize the domain of the Hamiltonian of this model, and establish the validity of the Tan relations for all wave functions in the domain.}, author = {Moser, Thomas and Seiringer, Robert}, issn = {00103616}, journal = {Communications in Mathematical Physics}, number = {1}, pages = {329 -- 355}, publisher = {Springer}, title = {{Stability of a fermionic N+1 particle system with point interactions}}, doi = {10.1007/s00220-017-2980-0}, volume = {356}, year = {2017}, } @article{743, abstract = {This special issue of the Journal on Formal Methods in System Design is dedicated to Prof. Helmut Veith, who unexpectedly passed away in March 2016. Helmut Veith was a brilliant researcher, inspiring collaborator, passionate mentor, generous friend, and valued member of the formal methods community. Helmut was not only known for his numerous and influential contributions in the field of automated verification (most prominently his work on Counterexample-Guided Abstraction Refinement [1,2]), but also for his untiring and passionate efforts for the logic community: he co-organized the Vienna Summer of Logic (an event comprising twelve conferences and numerous workshops which attracted thousands of researchers from all over the world), he initiated the Vienna Center for Logic and Algorithms (which promotes international collaboration on logic and algorithms and organizes outreach events such as the LogicLounge), and he coordinated the Doctoral Program on Logical Methods in Computer Science at TU Wien (currently educating more than 40 doctoral students) and a National Research Network on Rigorous Systems Engineering (uniting fifteen researchers in Austria to address the challenge of building reliable and safe computer systems). With his enthusiasm and commitment, Helmut completely reshaped the Austrian research landscape in the field of logic and verification in his few years as a full professor at TU Wien.}, author = {Gottlob, Georg and Henzinger, Thomas A and Weißenbacher, Georg}, journal = {Formal Methods in System Design}, number = {2}, pages = {267 -- 269}, publisher = {Springer}, title = {{Preface of the special issue in memoriam Helmut Veith}}, doi = {10.1007/s10703-017-0307-6}, volume = {51}, year = {2017}, } @article{744, abstract = {In evolutionary game theory interactions between individuals are often assumed obligatory. However, in many real-life situations, individuals can decide to opt out of an interaction depending on the information they have about the opponent. We consider a simple evolutionary game theoretic model to study such a scenario, where at each encounter between two individuals the type of the opponent (cooperator/defector) is known with some probability, and where each individual either accepts or opts out of the interaction. If the type of the opponent is unknown, a trustful individual accepts the interaction, whereas a suspicious individual opts out of the interaction. If either of the two individuals opt out both individuals remain without an interaction. We show that in the prisoners dilemma optional interactions along with suspicious behaviour facilitates the emergence of trustful cooperation.}, author = {Priklopil, Tadeas and Chatterjee, Krishnendu and Nowak, Martin}, issn = {00225193}, journal = { Journal of Theoretical Biology}, pages = {64 -- 72}, publisher = {Elsevier}, title = {{Optional interactions and suspicious behaviour facilitates trustful cooperation in prisoners dilemma}}, doi = {10.1016/j.jtbi.2017.08.025}, volume = {433}, year = {2017}, } @article{745, abstract = {Fluid flows in nature and applications are frequently subject to periodic velocity modulations. Surprisingly, even for the generic case of flow through a straight pipe, there is little consensus regarding the influence of pulsation on the transition threshold to turbulence: while most studies predict a monotonically increasing threshold with pulsation frequency (i.e. Womersley number, ), others observe a decreasing threshold for identical parameters and only observe an increasing threshold at low . In the present study we apply recent advances in the understanding of transition in steady shear flows to pulsating pipe flow. For moderate pulsation amplitudes we find that the first instability encountered is subcritical (i.e. requiring finite amplitude disturbances) and gives rise to localized patches of turbulence ('puffs') analogous to steady pipe flow. By monitoring the impact of pulsation on the lifetime of turbulence we map the onset of turbulence in parameter space. Transition in pulsatile flow can be separated into three regimes. At small Womersley numbers the dynamics is dominated by the decay turbulence suffers during the slower part of the cycle and hence transition is delayed significantly. As shown in this regime thresholds closely agree with estimates based on a quasi-steady flow assumption only taking puff decay rates into account. The transition point predicted in the zero limit equals to the critical point for steady pipe flow offset by the oscillation Reynolds number (i.e. the dimensionless oscillation amplitude). In the high frequency limit on the other hand, puff lifetimes are identical to those in steady pipe flow and hence the transition threshold appears to be unaffected by flow pulsation. In the intermediate frequency regime the transition threshold sharply drops (with increasing ) from the decay dominated (quasi-steady) threshold to the steady pipe flow level.}, author = {Xu, Duo and Warnecke, Sascha and Song, Baofang and Ma, Xingyu and Hof, Björn}, issn = {00221120}, journal = {Journal of Fluid Mechanics}, pages = {418 -- 432}, publisher = {Cambridge University Press}, title = {{Transition to turbulence in pulsating pipe flow}}, doi = {10.1017/jfm.2017.620}, volume = {831}, year = {2017}, } @article{746, abstract = {Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-Aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR. This correlated with a reduced amplitude of synaptic NMDAR currents, a lack of their mGluR5-Activated long-Term depression, and NMDAR/hippocampus dependent cognitive deficits. These synaptic and behavioral phenomena were reversed by knocking down Homer1a in Fmr1 KO mice. Our study provides a mechanistic link between changes of mGluR5 dynamics and pathological phenotypes of FXS, unveiling novel targets for mGluR5-based therapeutics.}, author = {Aloisi, Elisabetta and Le Corf, Katy and Dupuis, Julien and Zhang, Pei and Ginger, Melanie and Labrousse, Virginie and Spatuzza, Michela and Georg Haberl, Matthias and Costa, Lara and Shigemoto, Ryuichi and Tappe Theodor, Anke and Drago, Fillippo and Vincenzo Piazza, Pier and Mulle, Christophe and Groc, Laurent and Ciranna, Lucia and Catania, Maria and Frick, Andreas}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice}}, doi = {10.1038/s41467-017-01191-2}, volume = {8}, year = {2017}, }