Showing papers by "Collège de France published in 2012"

A Neuronal Model of Predictive Coding Accounting for the Mismatch Negativity

Abstract: The mismatch negativity (MMN) is thought to index the activation of specialized neural networks for active prediction and deviance detection. However, a detailed neuronal model of the neurobiological mechanisms underlying the MMN is still lacking, and its computational foundations remain debated. We propose here a detailed neuronal model of auditory cortex, based on predictive coding, that accounts for the critical features of MMN. The model is entirely composed of spiking excitatory and inhibitory neurons interconnected in a layered cortical architecture with distinct input, predictive, and prediction error units. A spike-timing dependent learning rule, relying upon NMDA receptor synaptic transmission, allows the network to adjust its internal predictions and use a memory of the recent past inputs to anticipate on future stimuli based on transition statistics. We demonstrate that this simple architecture can account for the major empirical properties of the MMN. These include a frequency-dependent response to rare deviants, a response to unexpected repeats in alternating sequences (ABABAA…), a lack of consideration of the global sequence context, a response to sound omission, and a sensitivity of the MMN to NMDA receptor antagonists. Novel predictions are presented, and a new magnetoencephalography experiment in healthy human subjects is presented that validates our key hypothesis: the MMN results from active cortical prediction rather than passive synaptic habituation.

Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo

Abstract: Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization and strength of their adherens junctions vary has not been demonstrated in vivo. Here we report that vascular endothelial cadherin, an endothelial specific adhesion protein located at adherens junctions, is phosphorylated in Y658 and Y685 in vivo in veins but not in arteries under resting conditions. This difference is due to shear stress-induced junctional Src activation in veins. Phosphorylated vascular endothelial-cadherin is internalized and ubiquitinated in response to permeability-increasing agents such as bradykinin and histamine. Inhibition of Src blocks vascular endothelial cadherin phosphorylation and bradykinin-induced permeability. Point mutation of Y658F and Y685F prevents vascular endothelial cadherin internalization, ubiquitination and an increase in permeability by bradykinin in vitro. Thus, phosphorylation of vascular endothelial cadherin contributes to a dynamic state of adherens junctions, but is not sufficient to increase vascular permeability in the absence of inflammatory agents.

Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex.

Abstract: Specific transfer of (orthodenticle homeobox 2) Otx2 homeoprotein into GABAergic interneurons expressing parvalbumin (PV) is necessary and sufficient to open, then close, a critical period (CP) of plasticity in the developing mouse visual cortex. The accumulation of endogenous Otx2 in PV cells suggests the presence of specific Otx2 binding sites. Here, we find that perineuronal nets (PNNs) on the surfaces of PV cells permit the specific, constitutive capture of Otx2. We identify a 15 aa domain containing an arginine-lysine doublet (RK peptide) within Otx2, bearing prototypic traits of a glycosaminoglycan (GAG) binding sequence that mediates Otx2 binding to PNNs, and specifically to chondroitin sulfate D and E, with high affinity. Accordingly, PNN hydrolysis by chondroitinase ABC reduces the amount of endogenous Otx2 in PV cells. Direct infusion of RK peptide similarly disrupts endogenous Otx2 localization to PV cells, reduces PV and PNN expression, and reopens plasticity in adult mice. The closure of one eye during this transient window reduces cortical acuity and is specific to the RK motif, as an Alanine-Alanine variant or a scrambled peptide fails to reactivate plasticity. Conversely, this transient reopening of plasticity in the adult restores binocular vision in amblyopic mice. Thus, one function of PNNs is to facilitate the persistent internalization of Otx2 by PV cells to maintain CP closure. The pharmacological use of the Otx2 GAG binding domain offers a novel, potent therapeutic tool with which to restore cortical plasticity in the mature brain.

Allostery and the Monod-Wyman-Changeux Model After 50 Years

Abstract: The Monod-Wyman-Changeux (MWC) model was conceived in 1965 to account for the signal transduction and cooperative properties of bacterial regulatory enzymes and hemoglobin. It was soon extended to pharmacological receptors for neurotransmitters and other macromolecular entities involved in intracellular and intercellular communications. Five decades later, the two main hypotheses of the model are reexamined on the basis of a variety of regulatory proteins with known X-ray structures: (a) Regulatory proteins possess an oligomeric structure with symmetry properties, and (b) the allosteric interactions between topographically distinct sites are mediated by a conformational transition established between a few preestablished states with conservation of symmetry and ligand-directed conformational selection. Several well-documented examples are adequately represented by the MWC model, yet a few possible exceptions are noted. New questions are raised concerning the dynamics of the allosteric transitions and more...

Generating entangled microwave radiation over two transmission lines.

Abstract: Using a superconducting circuit, the Josephson mixer, we demonstrate the first experimental realization of spatially separated two-mode squeezed states of microwave light. Driven by a pump tone, a first Josephson mixer generates, out of quantum vacuum, a pair of entangled fields at different frequencies on separate transmission lines. A second mixer, driven by a π-phase shifted copy of the first pump tone, recombines and disentangles the two fields. The resulting output noise level is measured to be lower than for the vacuum state at the input of the second mixer, an unambiguous proof of entanglement. Moreover, the output noise level provides a direct, quantitative measure of entanglement, leading here to the demonstration of 6 Mebit · s(-1) (mega entangled bits per second) generated by the first mixer.

Towards systems materials engineering.

Abstract: System-level planning of theoretical and experimental efforts is increasingly important for the development of modern materials science.

Search for gravitational waves from low mass compact binary coalescence in LIGO's sixth science run and Virgo's science runs 2 and 3

Abstract: We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M(circle dot); this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3 x 10(-4), 3.1 x 10(-5), and 6.4 x 10(-6) Mpc(-3) yr(-1), respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.

Deletion of Astroglial Connexins Weakens the Blood–Brain Barrier:

Abstract: Astrocytes, the most prominent glial cell type in the brain, send specialized processes named endfeet, which enwrap blood vessels and express a large molecular repertoire dedicated to the physiology of the vascular system. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein connexins 43 and 30 (Cx43 and Cx30) allowing for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. The contribution of astroglial connexins to the physiology of the brain vascular system has never been addressed. Here, we show that Cx43 and Cx30 expression at the level of perivascular endfeet starts from postnatal days 2 and 12 and is fully mature at postnatal days 15 and 20, respectively, indicating that astroglial perivascular connectivity occurs and develops during postnatal blood–brain barrier (BBB) maturation. We demonstrate that mice lacking Cx30 and Cx43 in GFAP (glial fibrillary acidic protein)-positive cells display astrocyte endfeet edema and a partial loss of the astroglial water channel aquaporin-4 and β-dystroglycan, a transmembrane receptor anchoring astrocyte endfeet to the perivascular basal lamina. Furthermore, the absence of astroglial connexins weakens the BBB, which opens upon increased hydrostatic vascular pressure and shear stress. These results demonstrate that astroglial connexins are necessary to maintain BBB integrity.

A Crypt-Specific Core Microbiota Resides in the Mouse Colon

Abstract: In an attempt to explore the microbial content of functionally critical niches of the mouse gastrointestinal tract, we targeted molecular microbial diagnostics of the crypts that contain the intestinal stem cells, which account for epithelial regener- ation. As current evidence indicates, the gut microbiota affects epithelial regeneration; bacteria that are likely to primarily par- ticipate in this essential step of the gut, microbiota cross talk, have been identified. We show in this article that only the cecal and colonic crypts harbor resident microbiota in the mouse and that regardless of the line and breeding origin of these mice, this bacterial population is unexpectedly dominated by aerobic genera. Interestingly, this microbiota resembles the restricted micro- biota found in the midgut of invertebrates; thus, the presence of our so-called "crypt-specific core microbiota" (CSCM) in the mouse colon potentially reflects a coevolutionary process under selective conditions that can now be addressed. We suggest that CSCM could play both a protective and a homeostatic role within the colon. This article is setting the bases for such studies, par- ticularly by providing a bona fide—and essentially cultivable—crypt microbiota of reference. IMPORTANCE Metagenomic typing of the whole-gut luminal microbiome was recently provided, revealing great opportunities for physiological and physiopathological analysis of the host-microbiota interface. On this basis, it appears increasingly important to analyze which niches of the gut exposed to a particular microbiota are of major functional importance, specifically focusing on the crypt, which accounts for permanent epithelial renewal, and to analyze how this microbiota compares to its luminal counterpart in composition and quantity. Crypt-specific core microbiotas may show themselves as important elements regard- ing crypt protection and homeostasis of its functions.

Noradrenergic Neurons of the Locus Coeruleus Are Phase Locked to Cortical Up-Down States during Sleep

Abstract: Nonrapid eye movement (NREM) sleep is characterized by periodic changes in cortical excitability that are reflected in the electroencephalography (EEG) as high-amplitude slow oscillations, indicative ofcortical Up/Downstates.These slowoscillations arethoughttobe involved in NREM sleep-dependent memory consolidation. Although thelocuscoeruleus(LC)noradrenergicsystemisknowntoplayarole inoff-linememoryconsolidation(thatmayoccurduringNREMsleep), cortico--coerulear interactions during NREM sleep have not yet been studied in detail. Here, we investigated the timing of LC spikes as a function of sleep-associated slow oscillations. Cortical EEG was monitored,alongwithactivityofLCneuronsrecordedextracellularly, in nonanesthetized naturally sleeping rats. LC spike-triggered averaging of EEG, together with phase-locking analysis, revealed preferential firing of LC neurons along the ascending edge of the EEG slow oscillation, correlating with Down-to-Up state transition. LC neurons were locked best when spikes were shifted forward ~50 ms in time with respect to the EEG slow oscillation. These results suggest that during NREM sleep, firing of LC neurons may contribute to the rising phase of the EEG slow wave by providing a neuromodulatory input that increases cortical excitability, thereby promoting plasticity within these circuits.

Green Microwave Synthesis of MIL‐100(Al, Cr, Fe) Nanoparticles for Thin‐Film Elaboration

Abstract: Nanoparticles of mesoporous MIL-100(Al, Cr or Fe) metal–organic frameworks were synthesized by a microwave-assisted solvothermal route with green solvents. The optimization of yield, crystallinity, and particle size was achieved through the control of synthetic parameters such as temperature, heating rate, and dwelling time. The particle size strongly depends on the metallic cation and the metal and linker precursors; nanoparticles smaller than 100 nm were obtained for iron and chromium based MIL-100. Finally, stable colloidal solutions of iron and chromium MIL-100 nanoparticles were used for thin layer dip-coating deposition, which resulted in high optical quality thin films, the porosity of which was investigated by environmental ellipsometric porosimetry.

Resilience of the spectral standard model

Abstract: We show that the inconsistency between the spectral Standard Model and the experimental value of the Higgs mass is resolved by the presence of a real scalar field strongly coupled to the Higgs field. This scalar field was already present in the spectral model and we wrongly neglected it in our previous computations. It was shown recently by several authors, independently of the spectral approach, that such a strongly coupled scalar field stabilizes the Standard Model up to unification scale in spite of the low value of the Higgs mass. In this letter we show that the noncommutative neutral singlet modifies substantially the RG analysis, invalidates our previous prediction of Higgs mass in the range 160-180 Gev, and restores the consistency of the noncommutative geometric model with the low Higgs mass.

Semaphorin3A, Neuropilin-1, and PlexinA1 Are Required for Lymphatic Valve Formation

Abstract: Rationale:The lymphatic vasculature plays a major role in fluid homeostasis, absorption of dietary lipids, and immune surveillance. Fluid transport depends on the presence of intraluminal valves within lymphatic collectors. Defective formation of lymphatic valves leads to lymphedema, a progressive and debilitating condition for which curative treatments are currently unavailable. How lymphatic valve formation is regulated remains largely unknown. Objective:We investigated if the repulsive axon guidance molecule Semaphorin3A (Sema3A) plays a role in lymphatic valve formation. Methods and Results:We show that Sema3A mRNA is expressed in lymphatic vessels and that Sema3A protein binds to lymphatic valves expressing the Neuropilin-1 (Nrp1) and PlexinA1 receptors. Using mouse knockout models, we show that Sema3A is selectively required for lymphatic valve formation, via interaction with Nrp1 and PlexinA1. Sema3a−/− mice exhibit defects in lymphatic valve formation, which are not due to abnormal lymphatic patte...

Protection Against Myocardial Infarction and No-Reflow Through Preservation of Vascular Integrity by Angiopoietin-Like 4

Abstract: Background—Increased permeability, predominantly controlled by endothelial junction stability, is an early event in the deterioration of vascular integrity in ischemic disorders. Hemorrhage, edema, and inflammation are the main features of reperfusion injuries, as observed in acute myocardial infarction (AMI). Thus, preservation of vascular integrity is fundamental in ischemic heart disease. Angiopoietins are pivotal modulators of cell–cell junctions and vascular integrity. We hypothesized that hypoxic induction of angiopoietin-like protein 4 (ANGPTL4) might modulate vascular damage, infarct size, and no-reflow during AMI. Methods and Results—We showed that vascular permeability, hemorrhage, edema, inflammation, and infarct severity were increased in angptl4-deficient mice. We determined that decrease in vascular endothelial growth factor receptor 2 (VEGFR2) and VE-cadherin expression and increase in Src kinase phosphorylation downstream of VEGFR2 were accentuated after ischemia-reperfusion in the coronar...

In vivo optical imaging with rare earth doped Ca_2Si_5N_8 persistent luminescence nanoparticles

Abstract: Ca2Si5N8:Eu2+,Tm3+ presents outstanding long lasting luminescence at about 610 nm. However, to be useful for in vivo optical imaging, persistent luminescence materials should possess high optical performance combined with sizes in the nanoscale. With this aim, we investigated two different techniques for the preparation of nanoparticles from Ca2Si5N8:Eu2+,Tm3+ bulk powder. First, nanoparticles were successfully prepared with the pulsed laser ablation method in liquid (abbreviated as PLAL). Secondly, nanoparticles obtained by selective sedimentation from the bulk compound resulted in satisfactory yield and allowed to perform the first real-time in vivo imaging with Ca2Si5N8:Eu2+,Tm3+ host. Finally the influence of surface functionalization on the biodistribution of the probe after systemic injection is discussed.

Field Locked to a Fock State by Quantum Feedback with Single Photon Corrections

Abstract: Quantum feedback is a promising tool for preparing and protecting a quantum state. It drives a quantum system towards a target state by the repeated action of a sensorcontroller-actuator loop. Nevertheless its experimental implementation is very challenging, as it must overcome a fundamental difficulty: the sensor measurement causes a random backaction on the system. We have implemented a continuous quantum feedback protocol in the context of cavity quantum electrodynamics. The system to be controlled is a mode of the electromagnetic field confined in a very high finesse microwave cavity in the Fabry-Perot configuration. Circular Rydberg atoms interacting dispersively with the field serve as sensors. They perform quantum non-demolition measurements of the photon number. Knowing the results of these measurements, and knowing all the experimental imperfections, a classical computer estimates in real time the field state. It then commands the preparation of resonant circular Rydberg atoms to absorb or to emit photons in order to stabilize the field around target Fock state. In this way, we have been able to prepare on demand and protect Fock states containing 1 to 7 photons.

Targeted high-throughput sequencing for diagnosis of genetically heterogeneous diseases: efficient mutation detection in Bardet-Biedl and Alström Syndromes

Abstract: Background Bardet-Biedl syndrome (BBS) is a pleiotropic recessive disorder that belongs to the rapidly growing family of ciliopathies. It shares phenotypic traits with other ciliopathies, such as Alstrom syndrome (ALMS), nephronophthisis (NPHP) or Joubert syndrome. BBS mutations have been detected in 16 different genes ( BBS1 - BBS16 ) without clear genotype-to-phenotype correlation. This extensive genetic heterogeneity is a major concern for molecular diagnosis and genetic counselling. While various strategies have been recently proposed to optimise mutation detection, they either fail to detect mutations in a majority of patients or are time consuming and costly. Method We tested a targeted exon-capture strategy coupled with multiplexing and high-throughput sequencing on 52 patients: 14 with known mutations as proof-of-principle and 38 with no previously detected mutation. Thirty genes were targeted in total including the 16 BBS genes, the 12 known NPHP genes, the single ALMS gene ALMS1 and the proposed modifier CCDC28B . Results This strategy allowed the reliable detection of causative mutations (including homozygous/heterozygous exon deletions) in 68% of BBS patients without previous molecular diagnosis and in all proof-of-principle samples. Three probands carried homozygous truncating mutations in ALMS1 confirming the major phenotypic overlap between both disorders. The efficiency of detecting mutations in patients was positively correlated with their compliance with the classical BBS phenotype (mutations were identified in 81% of ‘classical’ BBS patients) suggesting that only a few true BBS genes remain to be identified. We illustrate some interpretation problems encountered due to the multiplicity of identified variants. Conclusion This strategy is highly efficient and cost effective for diseases with high genetic heterogeneity, and guarantees a quality of coverage in coding sequences of target genes suited for diagnosis purposes.

Imagining Being Somewhere Else: Neural Basis of Changing Perspective in Space

Abstract: The capacity to imagine being somewhere else and seeing the environment from a different point of view is crucial for spatial planning in daily life and for understanding the intentions, actions, and state of mind of other people. The neural bases of spatial updating of multiple object locations were investigated using functional magnetic resonance imaging. Healthy volunteers saw an array of objects on a table in a virtual reality environment and imagined movement of their own viewpoint or rotation of the array. Their memory for the locations of the objects was then tested with a change-detection task. Behavioral results confirmed the advantage for imagined viewpoint change compared with imagined array rotation of equivalent size. Encoding of object locations was associated with a network of areas, including bilateral superior and inferior parietal cortices. The precuneus was additionally activated by the demands of both viewpoint- and array rotation. The parieto-occipital sulcus/retrosplenial cortex and hippocampus were additionally activated by the demands of viewpoint rotation, while array rotation was associated with activation of the right intraparietal sulcus. These findings support a computational model of spatial memory in which parieto-occipital sulcus/retrosplenial cortex mediates spatial updating as part of a process of translation between "egocentric" and "allocentric" reference frames.

The second-order luminosity-redshift relation in a generic inhomogeneous cosmology

Abstract: After recalling a general non-perturbative expression for the luminosity-redshift relation holding in a recently proposed ``geodesic light-cone" gauge, we show how it can be transformed to phenomenologically more convenient gauges in which cosmological perturbation theory is better understood. We present, in particular, the complete result on the luminosity-redshift relation in the Poisson gauge up to second order for a fairly generic perturbed cosmology, assuming that appreciable vector and tensor perturbations are only generated at second order. This relation provides a basic ingredient for the computation of the effects of stochastic inhomogeneities on precision dark-energy cosmology whose results we have anticipated in a recent letter. More generally, it can be used in connection with any physical information carried by light-like signals traveling along our past light-cone.

Critical aspects in the production of periodically ordered mesoporous titania thin films

Abstract: Periodically ordered mesoporous titania thin films (MTTF) present a high surface area, controlled porosity in the 2–20 nm pore diameter range and an amorphous or crystalline inorganic framework. These materials are nowadays routinely prepared by combining soft chemistry and supramolecular templating. Photocatalytic transparent coatings and titania-based solar cells are the immediate promising applications. However, a wealth of new prospective uses have emerged on the horizon, such as advanced catalysts, perm-selective membranes, optical materials based on plasmonics and photonics, metamaterials, biomaterials or new magnetic nanocomposites. Current and novel applications rely on the ultimate control of the materials features such as pore size and geometry, surface functionality and wall structure. Even if a certain control of these characteristics has been provided by the methods reported so far, the needs for the next generation of MTTF require a deeper insight in the physical and chemical processes taking place in their preparation and processing. This article presents a critical discussion of these aspects. This discussion is essential to evolve from know-how to sound knowledge, aiming at a rational materials design of these fascinating systems.