TY - JOUR AB - Recent experiments have shown that motion detection in Drosophila starts with splitting the visual input into two parallel channels encoding brightness increments (ON) or decrements (OFF). This suggests the existence of either two (ON-ON, OFF-OFF) or four (for all pairwise interactions) separate motion detectors. To decide between these possibilities, we stimulated flies using sequences of ON and OFF brightness pulses while recording from motion-sensitive tangential cells. We found direction-selective responses to sequences of same sign (ON-ON, OFF-OFF), but not of opposite sign (ON-OFF, OFF-ON), refuting the existence of four separate detectors. Based on further measurements, we propose a model that reproduces a variety of additional experimental data sets, including ones that were previously interpreted as support for four separate detectors. Our experiments and the derived model mark an important step in guiding further dissection of the fly motion detection circuit. AU - Eichner, Hubert AU - Maximilian Jösch AU - Schnell, Bettina AU - Reiff, Dierk F AU - Borst, Alexander ID - 1299 IS - 6 JF - Neuron TI - Internal structure of the fly elementary motion detector VL - 70 ER - TY - JOUR AB - We propose a general conjecture for the mixed Hodge polynomial of the generic character varieties of representations of the fundamental group of a Riemann surface of genus g to GLn(C) with fixed generic semisimple conjugacy classes at k punctures. This conjecture generalizes the Cauchy identity for Macdonald polynomials and is a common generalization of two formulas that we prove in this paper. The first is a formula for the E-polynomial of these character varieties which we obtain using the character table of GLn(Fq). We use this formula to compute the Euler characteristic of character varieties. The second formula gives the Poincaré polynomial of certain associated quiver varieties which we obtain using the character table of gln(Fq). In the last main result we prove that the Poincaré polynomials of the quiver varieties equal certain multiplicities in the tensor product of irreducible characters of GLn(Fq). As a consequence we find a curious connection between Kac-Moody algebras associated with comet-shaped, and typically wild, quivers and the representation theory of GLn(Fq). AU - Tamas Hausel AU - Letellier, Emmanuel AU - Rodríguez Villegas, Fernando ID - 1467 IS - 2 JF - Duke Mathematical Journal TI - Arithmetic harmonic analysis on character and quiver varieties VL - 160 ER - TY - JOUR AB - The emergence of differences in the arrangement of cells is the first step towards the establishment of many organs. Understanding this process is limited by the lack of systematic characterization of epithelial organisation. Here we apply network theory at the scale of individual cells to uncover patterns in cell-to-cell contacts that govern epithelial organisation. We provide an objective characterisation of epithelia using network representation, where cells are nodes and cell contacts are links. The features of individual cells, together with attributes of the cellular network, produce a defining signature that distinguishes epithelia from different organs, species, developmental stages and genetic conditions. The approach permits characterization, quantification and classification of normal and perturbed epithelia, and establishes a framework for understanding molecular mechanisms that underpin the architecture of complex tissues. AU - Escudero, Luis M AU - Costa, Luciano AU - Anna Kicheva AU - Briscoe, James AU - Freeman, Matthew AU - Babu, Madan M ID - 1723 IS - 1 JF - Nature Communications TI - Epithelial organisation revealed by a network of cellular contacts VL - 2 ER - TY - JOUR AB - Morphogens, such as Decapentaplegic (Dpp) in the fly imaginal discs, form graded concentration profiles that control patterning and growth of developing organs. In the imaginal discs, proliferative growth is homogeneous in space, posing the conundrum of how morphogen concentration gradients could control position-independent growth. To understand the mechanism of proliferation control by the Dpp gradient, we quantified Dpp concentration and signaling levels during wing disc growth. Both Dpp concentration and signaling gradients scale with tissue size during development. On average, cells divide when Dpp signaling levels have increased by 50%. Our observations are consistent with a growth control mechanism based on temporal changes of cellular morphogen signaling levels. For a scaling gradient, this mechanism generates position-independent growth rates. AU - Wartlick, Ortrud AU - Mumcu, Peer AU - Anna Kicheva AU - Bittig, Thomas AU - Seum, Carole AU - Jülicher, Frank AU - González-Gaitán, Marcos A ID - 1724 IS - 6021 JF - Science TI - Dynamics of Dpp signaling and proliferation control VL - 331 ER - TY - JOUR AB - We report on a technique enabling electrical control of the contact silicidation process in silicon nanowire devices. Undoped silicon nanowires were contacted by pairs of nickel electrodes and each contact was selectively silicided by means of the Joule effect. By a realtime monitoring of the nanowire electrical resistance during the contact silicidation process we were able to fabricate nickel-silicide/silicon/nickel- silicide devices with controlled silicon channel length down to 8 nm. AU - Mongillo, Massimo AU - Spathis, Panayotis AU - Katsaros, Georgios AU - Gentile, Pascal AU - Sanquer, Marc AU - De Franceschi, Silvano ID - 1754 IS - 9 JF - ACS Nano TI - Joule-assisted silicidation for short-channel silicon nanowire devices VL - 5 ER - TY - JOUR AB - Spin-selective tunneling of holes in SiGe nanocrystals contacted by normal-metal leads is reported. The spin selectivity arises from an interplay of the orbital effect of the magnetic field with the strong spin-orbit interaction present in the valence band of the semiconductor. We demonstrate both experimentally and theoretically that spin-selective tunneling in semiconductor nanostructures can be achieved without the use of ferromagnetic contacts. The reported effect, which relies on mixing the light and heavy holes, should be observable in a broad class of quantum-dot systems formed in semiconductors with a degenerate valence band. AU - Georgios Katsaros AU - Golovach, Vitaly N AU - Spathis, Panayotis N AU - Ares, Natalia AU - Stoffel, Mathieu AU - Fournel, Frank AU - Schmidt, Oliver G AU - Glazman, Leonid I AU - De Franceschi, Silvano ID - 1755 IS - 24 JF - Physical Review Letters TI - Observation of spin-selective tunneling in sige nanocrystals VL - 107 ER - TY - CONF AB - Superconducting circuits have been successfully established as systems to prepare and investigate microwave light fields at the quantum level. In contrast to optical experiments where light is detected using photon counters, microwaves are usually measured with well developed linear amplifiers. This makes measurements of correlation functions - one of the important tools in optics - harder to achieve because they traditionally rely on photon counters and beam splitters. Here, we demonstrate a system where we can prepare on demand single microwave photons in a cavity and detect them at the two outputs of the cavity using linear amplifiers. Together with efficient data processing, this allows us to measure different observables of the cavity photons, including the first-order correlation function. Using these techniques we demonstrate cooling of a thermal background field in the cavity. AU - Bozyigit, Deniz AU - Lang, C AU - Steffen, L. Kraig AU - Johannes Fink AU - Eichler, Christopher AU - Baur, Matthias P AU - Bianchetti, R AU - Leek, Peter J AU - Filipp, Stefan AU - Wallraff, Andreas AU - Da Silva, Marcus P AU - Blais, Alexandre ID - 1776 IS - 1 TI - Correlation measurements of individual microwave photons emitted from a symmetric cavity VL - 264 ER - TY - JOUR AB - A wide range of experiments studying microwave photons localized in superconducting cavities have made important contributions to our understanding of the quantum properties of radiation. Propagating microwave photons, however, have so far been studied much less intensely. Here we present measurements in which we reconstruct the quantum state of itinerant single photon Fock states and their superposition with the vacuum by analyzing moments of the measured amplitude distribution up to fourth order. Using linear amplifiers and quadrature amplitude detectors, we have developed efficient methods to separate the detected single photon signal from the noise added by the amplifier. From our measurement data we have also reconstructed the corresponding Wigner function. AU - Eichler, Christopher AU - Bozyigit, Deniz AU - Lang, C AU - Steffen, L. AU - Fink, Johannes M AU - Wallraff, Andreas ID - 1777 IS - 22 JF - Physical Review Letters TI - Experimental state tomography of itinerant single microwave photons VL - 106 ER - TY - JOUR AB - Creating a train of single photons and monitoring its propagation and interaction is challenging in most physical systems, as photons generally interact very weakly with other systems. However, when confining microwave frequency photons in a transmission line resonator, effective photon-photon interactions can be mediated by qubits embedded in the resonator. Here, we observe the phenomenon of photon blockade through second-order correlation function measurements. The experiments clearly demonstrate antibunching in a continuously pumped source of single microwave photons measured by using microwave beam splitters, linear amplifiers, and quadrature amplitude detectors. We also investigate resonance fluorescence and Rayleigh scattering in Mollow-triplet-like spectra. AU - Lang, C AU - Bozyigit, Deniz AU - Eichler, Christopher AU - Steffen, L. Kraig AU - Johannes Fink AU - Abdumalikov, Abdufarrukh A AU - Baur, Matthias P AU - Filipp, Stefan AU - Da Silva, Marcus P AU - Blais, Alexandre AU - Wallraff, Andreas ID - 1778 IS - 24 JF - Physical Review Letters TI - Observation of resonant photon blockade at microwave frequencies using correlation function measurements VL - 106 ER - TY - JOUR AB - At optical frequencies the radiation produced by a source, such as a laser, a black body or a single-photon emitter, is frequently characterized by analysing the temporal correlations of emitted photons using single-photon counters. At microwave frequencies, however, there are no efficient single-photon counters yet. Instead, well-developed linear amplifiers allow for efficient measurement of the amplitude of an electromagnetic field. Here, we demonstrate first- and second-order correlation function measurements of a pulsed microwave-frequency single-photon source integrated on the same chip with a 50/50 beam splitter followed by linear amplifiers and quadrature amplitude detectors. We clearly observe single-photon coherence in first-order and photon antibunching in second-order correlation function measurements of the propagating fields. AU - Bozyigit, Deniz AU - Lang, C AU - Steffen, L. Kraig AU - Johannes Fink AU - Eichler, Christopher AU - Baur, Matthias P AU - Bianchetti, R AU - Leek, Peter J AU - Filipp, Stefan AU - Da Silva, Marcus P AU - Blais, Alexandre AU - Wallraff, Andreas ID - 1775 IS - 2 JF - Nature Physics TI - Antibunching of microwave-frequency photons observed in correlation measurements using linear detectors VL - 7 ER - TY - JOUR AB - Microwave cavities with high quality factors enable coherent coupling of distant quantum systems. Virtual photons lead to a transverse interaction between qubits when they are nonresonant with the cavity but resonant with each other. We experimentally investigate the inverse scaling of the interqubit coupling with the detuning from a cavity mode and its proportionality to the qubit-cavity interaction strength. We demonstrate that the enhanced coupling at higher frequencies is mediated by multiple higher-harmonic cavity modes. Moreover, we observe dark states of the coupled qubit-qubit system and analyze their relation to the symmetry of the applied driving field at different frequencies. AU - Filipp, Stefan AU - Göppl, M AU - Johannes Fink AU - Baur, Matthias P AU - Bianchetti, R AU - Steffen, L. Kraig AU - Wallraff, Andreas ID - 1781 IS - 6 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Multimode mediated qubit-qubit coupling and dark-state symmetries in circuit quantum electrodynamics VL - 83 ER - TY - JOUR AB - Continuous variable entanglement between two modes of a radiation field is usually studied at optical frequencies. Here we demonstrate experiments that show the entanglement between microwave photons of different energy in a broadband squeezed beam. We use a Josephson parametric amplifier to generate the two-mode correlated state and detect all four quadrature components simultaneously in a two-channel heterodyne setup using amplitude detectors. Analyzing two-dimensional phase space histograms for all possible pairs of quadratures allows us to determine the full covariance matrix, which is in good agreement with the one expected for a two-mode squeezed state. AU - Eichler, Christopher AU - Bozyigit, Deniz AU - Lang, C AU - Baur, Matthias P AU - Steffen, L. Kraig AU - Johannes Fink AU - Filipp, Stefan AU - Wallraff, Andreas ID - 1780 IS - 11 JF - Physical Review Letters TI - Observation of two-mode squeezing in the microwave frequency domain VL - 107 ER - TY - JOUR AB - Many membrane channels and receptors exhibit adaptive, or desensitized, response to a strong sustained input stimulus, often supported by protein activity-dependent inactivation. Adaptive response is thought to be related to various cellular functions such as homeostasis and enlargement of dynamic range by background compensation. Here we study the quantitative relation between adaptive response and background compensation within a modeling framework. We show that any particular type of adaptive response is neither sufficient nor necessary for adaptive enlargement of dynamic range. In particular a precise adaptive response, where system activity is maintained at a constant level at steady state, does not ensure a large dynamic range neither in input signal nor in system output. A general mechanism for input dynamic range enlargement can come about from the activity-dependent modulation of protein responsiveness by multiple biochemical modification, regardless of the type of adaptive response it induces. Therefore hierarchical biochemical processes such as methylation and phosphorylation are natural candidates to induce this property in signaling systems. AU - Tamar Friedlander AU - Brenner, Naama ID - 1815 IS - 2 JF - Mathematical Biosciences and Engineering TI - Adaptive response and enlargement of dynamic range VL - 8 ER - TY - JOUR AB - The Levene model is the simplest mathematical model to describe the evolution of gene frequencies in spatially subdivided populations. It provides insight into how locally varying selection promotes a population’s genetic diversity. Despite its simplicity, interesting problems have remained unsolved even in the diallelic case. In this paper we answer an open problem by establishing that for two alleles at one locus and J demes, up to 2J−1 polymorphic equilibria may coexist. We first present a proof for the case of stable monomorphisms and then show that the result also holds for protected alleles. These findings allow us to prove that any odd number (up to 2J−1) of equilibria is possible, before we extend the proof to even numbers. We conclude with some numerical results and show that for J>2, the proportion of parameter space affording this maximum is extremely small. AU - Sebastian Novak ID - 1863 IS - 3 JF - Theoretical Population Biology TI - The number of equilibria in the diallelic Levene model with multiple demes VL - 79 ER - TY - JOUR AB - Modern α-proteobacteria are thought to be closely related to the ancient symbiont of eukaryotes, an ancestor of mitochondria. Respiratory complex I from α-proteobacteria and mitochondria is well conserved at the level of the 14 "core" subunits, consistent with that notion. Mitochondrial complex I contains the core subunits, present in all species, and up to 31 "supernumerary" subunits, generally thought to have originated only within eukaryotic lineages. However, the full protein composition of an α-proteobacterial complex I has not been established previously. Here, we report the first purification and characterization of complex I from the α-proteobacterium Paracoccus denitrificans. Single particle electron microscopy shows that the complex has a well defined L-shape. Unexpectedly, in addition to the 14 core subunits, the enzyme also contains homologues of three supernumerary mitochondrial subunits as follows: B17.2, AQDQ/18, and 13 kDa (bovine nomenclature). This finding suggests that evolution of complex I via addition of supernumerary or "accessory" subunits started before the original endosymbiotic event that led to the creation of the eukaryotic cell. It also provides further confirmation that α-proteobacteria are the closest extant relatives of mitochondria. AU - Yip, Chui Y AU - Harbour, Michael E AU - Jayawardena, Kamburapola G AU - Fearnley, Ian M AU - Leonid Sazanov ID - 1975 IS - 7 JF - Journal of Biological Chemistry TI - Evolution of respiratory complex I "Supernumerary" subunits are present in the α-proteobacterial enzyme VL - 286 ER - TY - JOUR AB - Complex I is the first and largest enzyme of the respiratory chain, coupling electron transfer between NADH and ubiquinone to the translocation of four protons across the membrane. It has a central role in cellular energy production and has been implicated in many human neurodegenerative diseases. The L-shaped enzyme consists of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 Ã. resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-like subunits L, M and N is novel, with two inverted structural repeats of five transmembrane helices arranged, unusually, face-to-back. Each repeat includes a discontinuous transmembrane helix and forms half of a channel across the membrane. A network of conserved polar residues connects the two half-channels, completing the proton translocation pathway. Unexpectedly, lysines rather than carboxylate residues act as the main elements of the proton pump in these subunits. The fourth probable proton-translocation channel is at the interface of subunits N, K, J and A. The structure indicates that proton translocation in complex I, uniquely, involves coordinated conformational changes in six symmetrical structural elements. AU - Efremov, Rouslan G AU - Leonid Sazanov ID - 1973 IS - 7361 JF - Nature TI - Structure of the membrane domain of respiratory complex i VL - 476 ER - TY - JOUR AB - Complex I is the first enzyme of the respiratory chain and plays a central role in cellular energy production. It has been implicated in many human neurodegenerative diseases, as well as in ageing. One of the biggest membrane protein complexes, it is an L-shaped assembly consisting of hydrophilic and membrane domains. Previously, we have determined structures of the hydrophilic domain in several redox states. Last year was marked by fascinating breakthroughs in the understanding of the complete structure. We described the architecture of the membrane domain and of the entire bacterial complex I. X-ray analysis of the larger mitochondrial enzyme has also been published. The core subunits of the bacterial and mitochondrial enzymes have remarkably similar structures. The proposed mechanism of coupling between electron transfer and proton translocation involves long-range conformational changes, coordinated in part by a long α-helix, akin to the coupling rod of a steam engine. AU - Efremov, Rouslan G AU - Leonid Sazanov ID - 1974 IS - 4 JF - Current Opinion in Structural Biology TI - Respiratory complex I: 'steam engine' of the cell? VL - 21 ER - TY - JOUR AB - In Escherichia coli, the pole-to-pole oscillation of the Min proteins directs septum formation to midcell, which is required for symmetric cell division. In vitro, protein waves emerge from the self-organization of MinD, a membrane-binding ATPase, and its activator MinE. For wave propagation, the proteins need to cycle through states of collective membrane binding and unbinding. Although MinD presumably undergoes cooperative membrane attachment, it is unclear how synchronous detachment is coordinated. We used confocal and single-molecule microscopy to elucidate the order of events during Min wave propagation. We propose that protein detachment at the rear of the wave, and the formation of the E-ring, are accomplished by two complementary processes: first, local accumulation of MinE due to rapid rebinding, leading to dynamic instability; and second, a structural change induced by membrane-interaction of MinE in an equimolar MinD-MinE (MinDE) complex, which supports the robustness of pattern formation. AU - Martin Loose AU - Fischer-Friedrich, Elisabeth AU - Herold, Christoph AU - Kruse, Karsten AU - Schwille, Petra ID - 1985 IS - 5 JF - Nature Structural and Molecular Biology TI - Min protein patterns emerge from rapid rebinding and membrane interaction of MinE VL - 18 ER - TY - JOUR AB - One of the most fundamental features of biological systems is probably their ability to self-organize in space and time on different scales. Despite many elaborate theoretical models of how molecular self-organization can come about, only a few experimental systems of biological origin have so far been rigorously described, due mostly to their inherent complexity. The most promising strategy of modern biophysics is thus to identify minimal biological systems showing self-organized emergent behavior. One of the best-understood examples of protein self-organization, which has recently been successfully reconstituted in vitro, is represented by the oscillations of the Min proteins in Escherichia coli. In this review, we summarize the current understanding of the mechanism of Min protein self-organization in vivo and in vitro. We discuss the potential of the Min oscillations to sense the geometry of the cell and suggest that spontaneous protein waves could be a general means of intracellular organization. We hypothesize that cooperative membrane binding and unbinding, e.g., as an energy-dependent switch, may act as an important regulatory mechanism for protein oscillations and pattern formation in the cell. AU - Martin Loose AU - Kruse, Karsten AU - Schwille, Petra ID - 1986 IS - 1 JF - Annual Review of Biophysics TI - Protein self-organization: Lessons from the min system VL - 40 ER - TY - JOUR AB - Many species have morphologically and genetically differentiated sex chromosomes, such as the XY pair of mammals. Y chromosomes are often highly degenerated and carry few functional genes, so that XY males have only one copy of most Xlinked genes (whereas females have two). As a result, chromosome-wide mechanisms of dosage compensation, such as the mammalian X-inactivation, often evolve to reestablish expression balance. A similar phenomenon is expected in femaleheterogametic species, where ZW females should suffer from imbalances due to W-chromosome degeneration. However, no global dosage compensation mechanisms have been detected in the two independent ZW systems that have been studied systematically (birds and silkworm), leading to the suggestion that lack of global dosage compensation may be a general feature of female-heterogametic species. However, analyses of other independently evolved ZW systems are required to test if this is the case. In this study, we use published genomic and expression data to test for the presence of global dosage compensation in Schistosoma mansoni, a trematode parasite that causes schistosomiasis in humans. We find that Z-linked expression is reduced relative to autosomal expression in females but not males, consistent with incomplete or localized dosage compensation. This gives further support to the theory that female-heterogametic species may not require global mechanisms of dosage compensation. AU - Vicoso, Beatriz AU - Bachtrog, Doris ID - 2072 IS - 1 JF - Genome Biology and Evolution TI - Lack of global dosage compensation in Schistosoma mansoni, a female-heterogametic parasite VL - 3 ER -