119 research outputs found

    Analog Simulation of Weyl Particles with Cold Atoms

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    We study theoretically, numerically, and experimentally the relaxation of a collisionless gas in a quadrupole trap after a momentum kick. The non-separability of the potential enables a quasi thermalization of the single particle distribution function even in the absence of interactions. Suprinsingly, the dynamics features an effective decoupling between the strong trapping axis and the weak trapping plane. The energy delivered during the kick is redistributed according to the symmetries of the system and satisfies the Virial theorem, allowing for the prediction of the final temperatures. We show that this behaviour is formally equivalent to the relaxation of massless relativistic Weyl fermions after a sudden displacement from the center of a harmonic trap

    Invariant template matching in systems with spatiotemporal coding: a vote for instability

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    We consider the design of a pattern recognition that matches templates to images, both of which are spatially sampled and encoded as temporal sequences. The image is subject to a combination of various perturbations. These include ones that can be modeled as parameterized uncertainties such as image blur, luminance, translation, and rotation as well as unmodeled ones. Biological and neural systems require that these perturbations be processed through a minimal number of channels by simple adaptation mechanisms. We found that the most suitable mathematical framework to meet this requirement is that of weakly attracting sets. This framework provides us with a normative and unifying solution to the pattern recognition problem. We analyze the consequences of its explicit implementation in neural systems. Several properties inherent to the systems designed in accordance with our normative mathematical argument coincide with known empirical facts. This is illustrated in mental rotation, visual search and blur/intensity adaptation. We demonstrate how our results can be applied to a range of practical problems in template matching and pattern recognition.Comment: 52 pages, 12 figure

    Effect of Oxidative Stress on Homer Scaffolding Proteins

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    Homer proteins are a family of multifaceted scaffolding proteins that participate in the organization of signaling complexes at the post-synaptic density and in a variety of tissues including striated muscle. Homer isoforms form multimers via their C-terminal coiled coil domains, which allows for the formation of a polymeric network in combination with other scaffolding proteins. We hypothesized that the ability of Homer isoforms to serve as scaffolds would be influenced by oxidative stress. We have found by standard SDS-PAGE of lysates from adult mouse skeletal muscle exposed to air oxidation that Homer migrates as both a dimer and monomer in the absence of reducing agents and solely as a monomer in the presence of a reducing agent, suggesting that Homer dimers exposed to oxidation could be modified by the presence of an inter-molecular disulfide bond. Analysis of the peptide sequence of Homer 1b revealed the presence of only two cysteine residues located adjacent to the C-terminal coiled-coil domain. HEK 293 cells were transfected with wild-type and cysteine mutant forms of Homer 1b and exposed to oxidative stress by addition of menadione, which resulted in the formation of disulfide bonds except in the double mutant (C246G, C365G). Exposure of myofibers from adult mice to oxidative stress resulted in decreased solubility of endogenous Homer isoforms. This change in solubility was dependent on disulfide bond formation. In vitro binding assays revealed that cross-linking of Homer dimers enhanced the ability of Homer 1b to bind Drebrin, a known interacting partner. Our results show that oxidative stress results in disulfide cross-linking of Homer isoforms and loss of solubility of Homer scaffolds. This suggests that disulfide cross-linking of a Homer polymeric network may contribute to the pathophysiology seen in neurodegenerative diseases and myopathies characterized by oxidative stress

    MPP+-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress

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    Accumulating evidence suggests that endogenous dopamine may act as a neurotoxin and thereby participate in the pathophysiology of Parkinson’s disease (PD). Cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of PD due to its ability to generate reactive oxygen species (ROS). Inhibition of COX-2 leads to neuroprotection by preventing the formation of dopamine-quinone. In this study, we examined whether dopamine mediates 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in primary ventral mesencephalic (VM) neurons, an in vitro model of PD, and if so, whether the protective effects of COX-2 inhibitors on dopamine mediated MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis result from the reduction of ROS. Reserpine, a dopamine-depleting agent, significantly reduced VM neurotoxicity induced by MPP+, whereas dopamine had an additive effect on MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis. However, inhibition of COX-2 by a selective COX-2 inhibitor (DFU) or ibuprofen significantly attenuated MPP+-induced VM cell toxicity and VM dopaminergic cell apoptosis, which was accompanied by a decrease in ROS production in VM dopaminergic neurons. These results suggest that dopamine itself mediates MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis in the presence of COX-2

    Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

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    Background:Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Methods: Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. Results: A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Conclusions: Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology

    Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A "central hub" in schizophrenia pathophysiology?

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    Accumulating evidence points to altered GABAergic parvalbumin-expressing interneurons and impaired myelin/axonal integrity in schizophrenia. Both findings could be due to abnormal neurodevelopmental trajectories, affecting local neuronal networks and long-range synchrony and leading to cognitive deficits. In this review, we present data from animal models demonstrating that redox dysregulation, neuroinflammation and/or NMDAR hypofunction (as observed in patients) impairs the normal development of both parvalbumin interneurons and oligodendrocytes. These observations suggest that a dysregulation of the redox, neuroimmune, and glutamatergic systems due to genetic and early-life environmental risk factors could contribute to the anomalies of parvalbumin interneurons and white matter in schizophrenia, ultimately impacting cognition, social competence, and affective behavior via abnormal function of micro- and macrocircuits. Moreover, we propose that the redox, neuroimmune, and glutamatergic systems form a "central hub" where an imbalance within any of these "hub" systems leads to similar anomalies of parvalbumin interneurons and oligodendrocytes due to the tight and reciprocal interactions that exist among these systems. A combination of vulnerabilities for a dysregulation within more than one of these systems may be particularly deleterious. For these reasons, molecules, such as N-acetylcysteine, that possess antioxidant and anti-inflammatory properties and can also regulate glutamatergic transmission are promising tools for prevention in ultra-high risk patients or for early intervention therapy during the first stages of the disease

    Gelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion

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    The actin-binding protein, gelsolin, is a well known regulator of cancer cell invasion. However, the mechanisms by which gelsolin promotes invasion are not well established. As reactive oxygen species (ROS) have been shown to promote cancer cell invasion, we investigated on the hypothesis that gelsolin-induced changes in ROS levels may mediate the invasive capacity of colon cancer cells. Herein, we show that increased gelsolin enhances the invasive capacity of colon cancer cells, and this is mediated via gelsolin's effects in elevating intracellular superoxide (O2.-) levels. We also provide evidence for a novel physical interaction between gelsolin and Cu/ZnSOD, that inhibits the enzymatic activity of Cu/ZnSOD, thereby resulting in a sustained elevation of intracellular O2.-. Using microarray data of human colorectal cancer tissues from Gene Omnibus, we found that gelsolin gene expression positively correlates with urokinase plasminogen activator (uPA), an important matrix-degrading protease invovled in cancer invasion. Consistent with the in vivo evidence, we show that increased levels of O2.- induced by gelsolin overexpression triggers the secretion of uPA. We further observed reduction in invasion and intracellular O2.- levels in colon cancer cells, as a consequence of gelsolin knockdown using two different siRNAs. In these cells, concurrent repression of Cu/ZnSOD restored intracellular O2.- levels and rescued invasive capacity. Our study therefore identified gelsolin as a novel regulator of intracellular O2.- in cancer cells via interacting with Cu/ZnSOD and inhibiting its enzymatic activity. Taken together, these findings provide insight into a novel function of gelsolin in promoting tumor invasion by directly impacting the cellular redox milieu

    High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes

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    This work is supported by grants BIO2014- 57291-R from the Spanish Ministry of Economy and Competitiveness and “Plataforma de Recursos Biomoleculares y Bioinformáticos” PT13/0001/0007 from the ISCIII, both co-funded with European Regional Development Funds (ERDF); PROMETEOII/2014/025 from the Generalitat Valenciana (GVA-FEDER); Fundació la Marató TV3 (ref. 20133134); and EU H2020- INFRADEV-1-2015-1 ELIXIR-EXCELERATE (ref. 676559) and EU FP7-People ITN Marie Curie Project (ref 316861)

    Quasithermalization de fermions dans un potentiel quadrupolaire et refroidissement évaporatif d’un gaz de 40K jusqu’à la dégénérescence quantique

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    In this thesis we investigate experimentally the physics of a cold fermionic mixture consisting of 6Li and 40K. After a short description of the experimental apparatus and of a few technical particularities implemented during my PhD, for example the light-induced atomic desorption in the 2D-MOT by UV-light, we focus on two main observations of the fermionic nature of the gas.The first part describes the quasithermalization of 6Li in a magnetic quadrupole potential. Even though collisions are absent in a spin-polarized fermionic gas below a given temperature, the statistical ensemble undergoes energy redistribution after an excitation within the linear potential. We present an extensive experimental study as well as a comprehensive theoretical analysis. Moreover, the studied Hamiltonian can be canonically mapped onto a system of massless, harmonically trapped particles and the previously developed results are re-interpreted in order to describe this experimentally inaccessible system. A further development of the realized experiment allows even for the implementation of spin-orbit coupling in a gas of non-interacting fermions.In the second part, we describe the evaporative cooling of 40K to quantum degeneracy. Through different evaporative cooling stages we reach with a final number of 1.5e5 atoms in the ground-state a temperature of 62nK, which corresponds to 17% of the Fermi temperature.Dans cette thèse, nous avons étudié expérimentalement les propriétés physiques des fermions ultra-froids grâce à une machine conçue pour refroidir un mélange fermionique de 6Li et 40K. Après une courte description concernant la construction de l'expérience et quelques améliorations que j'ai implémentées pendant ma thèse (telles que la désorption atomique par lumière ultraviolette dans le 2D-MOT), l'exposé se concentre sur deux observations principales de l'origine fermionique des gaz de potassium et de lithium.La première partie présente la quasithermalization du 6Li dans un potentiel quadrupolaire, créé par un piège magnétique. Malgré l'absence de collisions dans un gaz fermionique polarisé en dessous d'une température donnée, nous observons une redistribution d'énergie dans l'ensemble statistique après une excitation dans le piège linéaire. Une étude expérimentale détaillée ainsi qu'une analyse théorique du phénomène sont présentées. De plus, une transformation canonique de l'hamiltonien du système permet la description de particules sans masses dans un piège harmonique. Les résultats expérimentaux du système réel (gaz 6Li dans un potentiel quadrupolaire) sont donc réinterprétés pour décrire ces particules non massiques, difficiles à observer. Un développement supplémentaire de notre système expérimental permet également la réalisation d'un couplage spin-orbite non-abélien dans le gaz fermionique sans interactions.Dans la deuxième partie, on décrit la réalisation d'un gaz dégénéré de 40K à l'aide du refroidissement évaporatif. Une succession d'étapes d'évaporation, utilisant différentes technologies de piégeage, nous permet d'obtenir 1.5e5 atomes dans l'état fondamental à une température de 62nK, température équivalente à 17% de la température de Fermi
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