Showing papers by "Collège de France published in 2013"

Superconducting circuits for quantum information: an outlook.

Abstract: The performance of superconducting qubits has improved by several orders of magnitude in the past decade. These circuits benefit from the robustness of superconductivity and the Josephson effect, and at present they have not encountered any hard physical limits. However, building an error-corrected information processor with many such qubits will require solving specific architecture problems that constitute a new field of research. For the first time, physicists will have to master quantum error correction to design and operate complex active systems that are dissipative in nature, yet remain coherent indefinitely. We offer a view on some directions for the field and speculate on its future.

Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation

Abstract: Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.

Porous boron nitride nanosheets for effective water cleaning

Abstract: Effective removal of oils, organic solvents and dyes from water is of significant, global importance for environmental and water source protection. Advanced sorbent materials with excellent sorption capacity need to be developed. Here we report porous boron nitride nanosheets with very high specific surface area that exhibit excellent sorption performances for a wide range of oils, solvents and dyes. The nanostructured material absorbs up to 33 times its own weight in oils and organic solvents while repelling water. The saturated boron nitride nanosheets can be readily cleaned for reuse by burning or heating in air because of their strong resistance to oxidation. This easy recyclability further demonstrates the potential of porous boron nitride nanosheets for water purification and treatment.

Nanoscaled metal borides and phosphides: recent developments and perspectives

Abstract: and Perspectives Sophie Carenco,†,‡,§,∥,⊥ David Portehault,*,†,‡,§ Ced́ric Boissier̀e,†,‡,§ Nicolas Meźailles, and Cleḿent Sanchez*,†,‡,§ †Chimie de la Matier̀e Condenseé de Paris, UPMC Univ Paris 06, UMR 7574, Colleg̀e de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France ‡Chimie de la Matier̀e Condenseé de Paris, CNRS, UMR 77574, Colleg̀e de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 05, France Chimie de la Matier̀e Condenseé de Paris, Colleg̀e de France, 11 Place Marcellin Berthelot, 75231 Paris Cedex 05, France Laboratory Heteroelements and Coordination, Chemistry Department, Ecole Polytechnique, CNRS-UMR 7653, Palaiseau, France

Engineering the Optical Response of the Titanium-MIL-125 Metal–Organic Framework through Ligand Functionalization

Abstract: Herein we discuss band gap modification of MIL-125, a TiO2/1,4-benzenedicarboxylate (bdc) metal–organic framework (MOF). Through a combination of synthesis and computation, we elucidated the electronic structure of MIL-125 with aminated linkers. The band gap decrease observed when the monoaminated bdc-NH2 linker was used arises from donation of the N 2p electrons to the aromatic linking unit, resulting in a red-shifted band above the valence-band edge of MIL-125. We further explored in silico MIL-125 with the diaminated linker bdc-(NH2)2 and other functional groups (−OH, −CH3, −Cl) as alternative substitutions to control the optical response. The bdc-(NH2)2 linking unit was predicted to lower the band gap of MIL-125 to 1.28 eV, and this was confirmed through the targeted synthesis of the bdc-(NH2)2-based MIL-125. This study illustrates the possibility of tuning the optical response of MOFs through rational functionalization of the linking unit, and the strength of combined synthetic/computational approach...

Biomimetic assembly and activation of [FeFe]-hydrogenases

Abstract: Hydrogenases are the most active molecular catalysts for hydrogen production and uptake1, 2, and could therefore facilitate the development of new types of fuel cell3, 4, 5. In [FeFe]-hydrogenases, catalysis takes place at a unique di-iron centre (the [2Fe] subsite), which contains a bridging dithiolate ligand, three CO ligands and two CN- ligands6, 7. Through a complex multienzymatic biosynthetic process, this [2Fe] subsite is first assembled on a maturation enzyme, HydF, and then delivered to the apo-hydrogenase for activation8. Synthetic chemistry has been used to prepare remarkably similar mimics of that subsite1, but it has failed to reproduce the natural enzymatic activities thus far. Here we show that three synthetic mimics (containing different bridging dithiolate ligands) can be loaded onto bacterial Thermotoga maritima HydF and then transferred to apo-HydA1, one of the hydrogenases of Chlamydomonas reinhardtii algae. Full activation of HydA1 was achieved only when using the HydF hybrid protein containing the mimic with an azadithiolate bridge, confirming the presence of this ligand in the active site of native [FeFe]-hydrogenases9, 10. This is an example of controlled metalloenzyme activation using the combination of a specific protein scaffold and active-site synthetic analogues. This simple methodology provides both new mechanistic and structural insight into hydrogenase maturation and a unique tool for producing recombinant wild-type and variant [FeFe]-hydrogenases, with no requirement for the complete maturation machinery

Solar fuels generation and molecular systems: is it homogeneous or heterogeneous catalysis?

Abstract: Catalysis is a key enabling technology for solar fuel generation. A number of catalytic systems, either molecular/homogeneous or solid/heterogeneous, have been developed during the last few decades for both the reductive and oxidative multi-electron reactions required for fuel production from water or CO2 as renewable raw materials. While allowing for a fine tuning of the catalytic properties through ligand design, molecular approaches are frequently criticized because of the inherent fragility of the resulting catalysts, when exposed to extreme redox potentials. In a number of cases, it has been clearly established that the true catalytic species is heterogeneous in nature, arising from the transformation of the initial molecular species, which should rather be considered as a pre-catalyst. Whether such a situation is general or not is a matter of debate in the community. In this review, covering water oxidation and reduction catalysts, involving noble and non-noble metal ions, we limit our discussion to the cases in which this issue has been directly and properly addressed as well as those requiring more confirmation. The methodologies proposed for discriminating homogeneous and heterogeneous catalysis are inspired in part by those previously discussed by Finke in the case of homogeneous hydrogenation reaction in organometallic chemistry [J. A. Widegren and R. G. Finke, J. Mol. Catal. A, 2003, 198, 317–341].

Spontaneous activation of [FeFe]-hydrogenases by an inorganic [2Fe] active site mimic

Abstract: Hydrogenases catalyze the formation of hydrogen. The cofactor ('H-cluster') of [FeFe]-hydrogenases consists of a [4Fe-4S] cluster bridged to a unique [2Fe] subcluster whose biosynthesis in vivo requires hydrogenase-specific maturases. Here we show that a chemical mimic of the [2Fe] subcluster can reconstitute apo-hydrogenase to full activity, independent of helper proteins. The assembled H-cluster is virtually indistinguishable from the native cofactor. This procedure will be a powerful tool for developing new artificial H₂-producing catalysts.

A Thermoelectric Heat Engine with Ultracold Atoms

Abstract: Thermoelectric effects, such as the generation of a particle current by a temperature gradient, have their origin in a reversible coupling between heat and particle flows. These effects are fundamental probes for materials and have applications to cooling and power generation. Here, we demonstrate thermoelectricity in a fermionic cold atoms channel in the ballistic and diffusive regimes, connected to two reservoirs. We show that the magnitude of the effect and the efficiency of energy conversion can be optimized by controlling the geometry or disorder strength. Our observations are in quantitative agreement with a theoretical model based on the Landauer-Buttiker formalism. Our device provides a controllable model system to explore mechanisms of energy conversion and realizes a cold atom–based heat engine.

Sustained production of ROS triggers compensatory proliferation and is required for regeneration to proceed

Abstract: A major issue in regenerative medicine is the role of injury in promoting cell plasticity. Here we explore the function of reactive oxygen species (ROS) induced through lesions in adult zebrafish. We show that ROS production, following adult fin amputation, is tightly regulated in time and space for at least 24 hours, whereas ROS production remains transient (2 hours) in mere wound healing. In regenerative tissue, ROS signaling triggers two distinct parallel pathways: one pathway is responsible for apoptosis, and the other pathway is responsible for JNK activation. Both events are involved in the compensatory proliferation of stump epidermal cells and are necessary for the progression of regeneration. Both events impact the Wnt, SDF1 and IGF pathways, while apoptosis only impacts progenitor marker expression. These results implicate oxidative stress in regeneration and provide new insights into the differences between healing and regeneration.

Water-mediated structuring of bone apatite

Abstract: It is well known that organic molecules from the vertebrate extracellular matrix of calcifying tissues are essential in structuring the apatite mineral. Here, we show that water also plays a structuring role. By using solid-state nuclear magnetic resonance, wide-angle X-ray scattering and cryogenic transmission electron microscopy to characterize the structure and organization of crystalline and biomimetic apatite nanoparticles as well as intact bone samples, we demonstrate that water orients apatite crystals through an amorphous calcium phosphate-like layer that coats the crystalline core of bone apatite. This disordered layer is reminiscent of those found around the crystalline core of calcified biominerals in various natural composite materials in vivo. This work provides an extended local model of bone biomineralization.

XLID-Causing Mutations and Associated Genes Challenged in Light of Data From Large-Scale Human Exome Sequencing

Abstract: Because of the unbalanced sex ratio (1.3–1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past. Such information is now available thanks to large-scale sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project, which provides variation information on 10,563 X chromosomes from the general population. We used this NHLBI cohort to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. We particularly question the implication in XLID of ten of them (AGTR2, MAGT1, ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which truncating variants or previously published mutations are observed at a relatively high frequency within this cohort. We also highlight 15 other genes (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3, RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted. We propose that similar reassessment of reported mutations (and genes) with the use of data from large-scale human exome sequencing would be relevant for a wide range of other genetic diseases.

Search for charged Higgs bosons : combined results using LEP data

Abstract: The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for pair-produced charged Higgs bosons in the framework of Two Higgs Doublet Models (2HDMs). The data of the four experiments are statistically combined. The results are interpreted within the 2HDM for Type I and Type II benchmark scenarios. No statistically significant excess has been observed when compared to the Standard Model background prediction, and the combined LEP data exclude large regions of the model parameter space. Charged Higgs bosons with mass below 80 GeV/c^2 (Type II scenario) or 72.5 GeV/c^2 (Type I scenario, for pseudo-scalar masses above 12 GeV/c^2) are excluded at the 95% confidence level.

Mutations of DEPDC5 cause autosomal dominant focal epilepsies

Abstract: The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.

Waveform Tomography Reveals Channeled Flow at the Base of the Oceanic Asthenosphere

Abstract: Understanding the relationship between different scales of convection that drive plate motions and hotspot volcanism still eludes geophysicists. Using full-waveform seismic tomography, we imaged a pattern of horizontally elongated bands of low shear velocity, most prominent between 200 and 350 kilometers depth, which extends below the well-developed low-velocity zone. These quasi-periodic fingerlike structures of wavelength ~2000 kilometers align parallel to the direction of absolute plate motion for thousands of kilometers. Below 400 kilometers depth, velocity structure is organized into fewer, undulating but vertically coherent, low-velocity plumelike features, which appear rooted in the lower mantle. This suggests the presence of a dynamic interplay between plate-driven flow in the low-velocity zone and active influx of low-rigidity material from deep mantle sources deflected horizontally beneath the moving top boundary layer.

How Bad Metals Turn Good: Spectroscopic Signatures of Resilient Quasiparticles

Abstract: We investigate transport in strongly correlated metals. Within dynamical mean-field theory, we calculate the resistivity, thermopower, optical conductivity and thermodynamic properties of a hole-doped Mott insulator. Two well-separated temperature scales are identified: ${T}_{\mathrm{FL}}$ below which Landau Fermi liquid behavior applies, and ${T}_{\mathrm{MIR}}$ above which the resistivity exceeds the Mott-Ioffe-Regel value and bad-metal behavior is found. We show that quasiparticle excitations remain well defined above ${T}_{\mathrm{FL}}$ and dominate transport throughout the intermediate regime ${T}_{\mathrm{FL}}\ensuremath{\lesssim}T\ensuremath{\lesssim}{T}_{\mathrm{MIR}}$. The lifetime of these resilient quasiparticles is longer for electronlike excitations and this pronounced particle-hole asymmetry has important consequences for the thermopower. The crossover into the bad-metal regime corresponds to the disappearance of these excitations and has clear signatures in optical spectroscopy.

New Insights into Bi2WO6 Properties as a Visible-Light Photocatalyst

Abstract: Bismuth tungstate has attractive photocatalytic properties under visible light. A better understanding of the origin of that good activity should allow its control and its optimization. An improved photocatalytic activity to different pollutants was obtained using bismuth-based oxide obtained by microwave-assisted synthesis combined with the addition of sodium dodecylsulfate as a size tailoring agent. It is shown using electron paramagnetic resonance that bismuth tungstate is able to generate hydroxyl radicals in aqueous aerated solution, but no superoxide radical anions are formed. The catalytic efficiency relative to TiO2 could be associated to differences in the number of excitons generated, to their lifetimes as holes and electrons in the semiconductor, and to valence and conduction band positions.

Symbolic capital and social classes

Abstract: In this short but dense piece, written for a special issue of the journal L'Arc devoted to the medieval historian Feorges Duby (whose sprawling oeuvre Bourdieu admired and drew on for its scrupulous genealogy of the mental-cum-social structure of the feudal triad of knight, priest, and peasant: see Georges Duby, The Three Orders (1982 [1978]), Bourdieu sums up and clarifies the core thesis of Distinction just as he was completing the book. This article is valuable for (1) stating forthrightly Bourdieu's conception of the 'double objectivity' of the social world and spotlighting the recursive constitution of social and mental structures; (2) stressing the performative capacity of symbolic forms and their multi-level implication in social struggles over and across social divisions; and (3) suggesting alluring parallels and obstinate differences between Bourdieu's 'genetic structuralism' and both the literary vision of Mercel Proust and the marginalist microsociology of Erving Goffman - two of his favorite mental 'sparring partners. 'In all, this article illuminates how Bourideu mingled Marx's sensuous materialism, Durkheim's teachings on classification (later extended by Cassirer), and Weber's insight into hierarchies of honor into a sociological model of class all his own - LW.

50 years of allosteric interactions: the twists and turns of the models

Abstract: The concept of allosteric interactions between topographically distinct sites, and the subsequent Monod-Wyman-Changeux model proposed in 1965 for the conformational change mediating them, arose around 50 years ago. Many classic regulatory proteins follow this model, which has been expanded and challenged over the years.

Direct imaging of topological edge states in cold-atom systems

Abstract: Detecting topological order in cold-atom experiments is an ongoing challenge, the resolution of which offers novel perspectives on topological matter. In material systems, unambiguous signatures of topological order exist for topological insulators and quantum Hall devices. In quantum Hall systems, the quantized conductivity and the associated robust propagating edge modes—guaranteed by the existence of nontrivial topological invariants—have been observed through transport and spectroscopy measurements. Here, we show that optical-lattice-based experiments can be tailored to directly visualize the propagation of topological edge modes. Our method is rooted in the unique capability for initially shaping the atomic gas and imaging its time evolution after suddenly removing the shaping potentials. Our scheme, applicable to an assortment of atomic topological phases, provides a method for imaging the dynamics of topological edge modes, directly revealing their angular velocity and spin structure.

Reaching fractional quantum Hall states with optical flux lattices.

Abstract: We present a robust scheme by which fractional quantum Hall states of bosons can be achieved for ultracold atomic gases. We describe a new form of optical flux lattice, suitable for commonly used atomic species with ground state angular momentum ${J}_{g}=1$, for which the lowest energy band is topological and nearly dispersionless. Through exact diagonalization studies, we show that, even for moderate interactions, the many-body ground states consist of bosonic fractional quantum Hall states, including the Laughlin state and the Moore-Read (Pfaffian) state. These phases are shown to have energy gaps that are larger than temperature scales achievable in ultracold gases.

How do astrocytes shape synaptic transmission? Insights from electrophysiology

Abstract: A major breakthrough in neuroscience has been the realization in the last decades that the dogmatic view of astroglial cells as being merely fostering and buffering elements of the nervous system is simplistic A wealth of investigations now shows that astrocytes actually participate in the control of synaptic transmission in an active manner This was first hinted by the intimate contacts glial processes make with neurons, particularly at the synaptic level, and evidenced using electrophysiological and calcium imaging techniques Calcium imaging has provided critical evidence demonstrating that astrocytic regulation of synaptic efficacy is not a passive phenomenon However, given that cellular activation is not only represented by calcium signaling, it is also crucial to assess concomitant mechanisms We and others have used electrophysiological techniques to simultaneously record neuronal and astrocytic activity, thus enabling the study of multiple ionic currents and in depth investigation of neuro-glial dialogues In the current review, we focus on the input such approach has provided in the understanding of astrocyte-neuron interactions underlying control of synaptic efficacy

Parameter estimation for compact binary coalescence signals with the first generation gravitational-wave detector network

Abstract: Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a "blind injection'' where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M(circle dot)-25M(circle dot) and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.

Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement

Abstract: Smoking is the most important preventable cause of mortality and morbidity worldwide. This nicotine addiction is mediated through the nicotinic acetylcholine receptor (nAChR), expressed on most neurons, and also many other organs in the body. Even within the ventral tegmental area (VTA), the key brain area responsible for the reinforcing properties of all drugs of abuse, nicotine acts on several different cell types and afferents. Identifying the precise action of nicotine on this microcircuit, in vivo, is important to understand reinforcement, and finally to develop efficient smoking cessation treatments. We used a novel lentiviral system to re-express exclusively high-affinity nAChRs on either dopaminergic (DAergic) or γ-aminobutyric acid-releasing (GABAergic) neurons, or both, in the VTA. Using in vivo electrophysiology, we show that, contrary to widely accepted models, the activation of GABA neurons in the VTA plays a crucial role in the control of nicotine-elicited DAergic activity. Our results demonstrate that both positive and negative motivational values are transmitted through the dopamine (DA) neuron, but that the concerted activity of DA and GABA systems is necessary for the reinforcing actions of nicotine through burst firing of DA neurons. This work identifies the GABAergic interneuron as a potential target for smoking cessation drug development.

A top-down synthesis route to ultrasmall multifunctional Gd-based silica nanoparticles for theranostic applications.

Abstract: New, ultrasmall nanoparticles with sizes below 5 nm have been obtained. These small rigid platforms (SRP) are composed of a polysiloxane matrix with DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid)-Gd3+ chelates on their surface. They have been synthesised by an original top-down process: 1) formation of a gadolinium oxide Gd2O3 core, 2) encapsulation in a polysiloxane shell grafted with DOTAGA ligands, 3) dissolution of the gadolinium oxide core due to chelation of Gd3+ by DOTAGA ligands and 4) polysiloxane fragmentation. These nanoparticles have been fully characterised using photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), a superconducting quantum interference device (SQUID) and electron paramagnetic resonance (EPR) to demonstrate the dissolution of the oxide core and by inductively coupled plasma mass spectrometry (ICP-MS), mass spectrometry, fluorescence spectroscopy, 29Si solid-state NMR, 1H NMR and diffusion ordered spectroscopy (DOSY) to determine the nanoparticle composition. Relaxivity measurements gave a longitudinal relaxivity r1 of 11.9 s−1 mM−1 per Gd at 60 MHz. Finally, potentiometric titrations showed that Gd3+ is strongly chelated to DOTAGA (complexation constant logβ110=24.78) and cellular tests confirmed the that nanoconstructs had a very low toxicity. Moreover, SRPs are excreted from the body by renal clearance. Their efficiency as contrast agents for MRI has been proved and they are promising candidates as sensitising agents for image-guided radiotherapy.

Average and dispersion of the luminosity-redshift relation in the concordance model

Abstract: Starting from the luminosity-redshift relation recently given up to second order in the Poisson gauge, we calculate the effects of the realistic stochastic background of perturbations of the so-called concordance model on the combined light-cone and ensemble average of various functions of the luminosity distance, and on their variance, as functions of redshift. We apply a gauge-invariant light-cone averaging prescription which is free from infrared and ultraviolet divergences, making our results robust with respect to changes of the corresponding cutoffs. Our main conclusions, in part already anticipated in a recent letter for the case of a perturbation spectrum computed in the linear regime, are that such inhomogeneities not only cannot avoid the need for dark energy, but also cannot prevent, in principle, the determination of its parameters down to an accuracy of order 10−3−10−5, depending on the averaged observable and on the regime considered for the power spectrum. However, taking into account the appropriate corrections arising in the non-linear regime, we predict an irreducible scatter of the data approaching the 10% level which, for limited statistics, will necessarily limit the attainable precision. The predicted dispersion appears to be in good agreement with current observational estimates of the distance-modulus variance due to Doppler and lensing effects (at low and high redshifts, respectively), and represents a challenge for future precision measurements.

A soft cortex is essential for asymmetric spindle positioning in mouse oocytes

Abstract: At mitosis onset, cortical tension increases and cells round up, ensuring correct spindle morphogenesis and orientation Thus, cortical tension sets up the geometric requirements of cell division On the contrary, cortical tension decreases during meiotic divisions in mouse oocytes, a puzzling observation because oocytes are round cells, stable in shape, that actively position their spindles We investigated the pathway leading to reduction in cortical tension and its significance for spindle positioning We document a previously uncharacterized Arp2/3-dependent thickening of the cortical F-actin essential for first meiotic spindle migration to the cortex Using micropipette aspiration, we show that cortical tension decreases during meiosis I, resulting from myosin-II exclusion from the cortex, and that cortical F-actin thickening promotes cortical plasticity These events soften and relax the cortex They are triggered by the Mos-MAPK pathway and coordinated temporally Artificial cortex stiffening and theoretical modelling demonstrate that a soft cortex is essential for meiotic spindle positioning

A gating mechanism of pentameric ligand-gated ion channels

Abstract: Pentameric ligand-gated ion channels (pLGICs) play a central role in intercellular communication in the nervous system and are involved in fundamental processes such as attention, learning, and memory. They are oligomeric protein assemblies that convert a chemical signal into an ion flux through the postsynaptic membrane, but the molecular mechanism of gating ions has remained elusive. Here, we present atomistic molecular dynamics simulations of the prokaryotic channels from Gloeobacter violaceus (GLIC) and Erwinia chrysanthemi (ELIC), whose crystal structures are thought to represent the active and the resting states of pLGICs, respectively, and of the eukaryotic glutamate-gated chloride channel from Caenorhabditis elegans (GluCl), whose open-channel structure was determined complexed with the positive allosteric modulator ivermectin. Structural observables extracted from the trajectories of GLIC and ELIC are used as progress variables to analyze the time evolution of GluCl, which was simulated in the absence of ivermectin starting from the structure with bound ivermectin. The trajectory of GluCl with ivermectin removed shows a sequence of structural events that couple agonist unbinding from the extracellular domain to ion-pore closing in the transmembrane domain. Based on these results, we propose a structural mechanism for the allosteric communication leading to deactivation/activation of the GluCl channel. This model of gating emphasizes the coupling between the quaternary twisting and the opening/closing of the ion pore and is likely to apply to other members of the pLGIC family.