1,354,123 research outputs found
Magneto-shear instability: a local Newtonian analysis
No full textMathematica notebook for calculating the dispersion relation of a Newtonian magneto-fluid in a background with shear and vorticity. The dispersion relation is written in terms of scalars built from the background quantities, as suitable for studying the impact of background gradients in a general setting.</span
Fluid-shear instability: a local Newtonian analysis
No full textMathematica notebook for calculating the dispersion relation of a Newtonian fluid in a background with shear and vorticity. The dispersion relation is written in terms of scalars built from the background quantities, as suitable for studying the impact of background gradients in a general setting.</span
Fluid-shear instability: a local Newtonian analysis
No full textMathematica notebook for calculating the dispersion relation of a Newtonian fluid in a background with shear and vorticity.
The dispersion relation is written in terms of scalars built from the background quantities, as suitable for studying the impact of background gradients in a general setting
Magneto-shear instability: a local Newtonian analysis
No full textMathematica notebook for calculating the dispersion relation of a Newtonian magneto-fluid in a background with shear and vorticity.
The dispersion relation is written in terms of scalars built from the background quantities, as suitable for studying the impact of background gradients in a general setting
COMBINING BIOINFORMATICS WITH WHOLE-CELL PATCH-CLAMP RECORDINGS TO INVESTIGATE THE ROLE OF αVβ3 INTEGRIN IN MOUSE MODELS OF ASD AND EPILEPSY
No full textAutism spectrum disorder (ASD) and epilepsy have a high degree of comorbidity. This co-occurrence is likely the result of underlying factors predisposing to both conditions. Integrins are heterodimeric receptors for extracellular matrix proteins and counter-receptors on adjacent cells. In the mouse brain, β3 integrin subunit pairs only with αV integrin subunit; loss of αV and β3 integrin subunits have been implicated in the onset of epilepsy and autism, respectively.
In this project, I investigate the effects of impairing αVβ3 integrin in the mouse cortex with the goal of identifying changes that may underlie both ASD and epilepsy, focusing on deficits in αVβ3 integrin receptor signalling at synapses.
I used AAV-mediated retrograde labelling in WT and constitutive Itgb3 KO mice to investigate the role of β3 integrin in dendritic spine number and morphology in corticopontine (CP) and commissural (COM) layer V pyramidal neurons of the medial prefrontal cortex (mPFC), two populations of pyramidal neurons that differ in terms of excitatory hodology. I found that COM neurons harboured more mushroom and fewer stubby spines compared to CP neurons in both WT and Itgb3 KO brains. Moreover, loss of β3 integrin induced a specific shortening of thin spines in CP neurons, hinting to a role of β3 integrin in immature spines.
In two different mouse models (a conditional KO for αV integrin and the constitutive KO for β3 integrin), I used comparative quantitative mass spectrometry of cortical synapses and bioinformatic protein-protein interaction (PPI) network analyses to identify genes involved in ASD and epilepsy. I found 19 proteins in common between Itgb3 and ItgaV PPI networks that were significantly changing in mass spectrometry analyses and were associated with ASD or epilepsy or both. Among these proteins, I focused of AMPA receptor (AMPAR) subunit GluA2, and group I metabotropic glutamate receptors mGluR1 and mGluR5 since they are involved in excitatory synaptic transmission.
In both mouse models, I recorded AMPAR excitatory synaptic currents in mPFC pyramidal neurons in the whole-cell patch clamp configuration upon pharmacological modulation of mGluR1/5 signalling. I isolated mGluR5 contribution using the selective antagonist MPEP in Itgb3 and ItgaV mouse models: MPEP treatment reduces AMPAR currents in both ItgaV KO and Itgb3 KO neurons. Loss of αVβ3 integrin affect selectivity mGluR5 regulation of AMPAR excitatory synaptic currents.
Since AMPAR phosphorylation affects receptor trafficking, I investigated whether mGluR5 inhibition affects AMPAR phosphorylation in cortices from WT and Itgb3 KO mice. MPEP treatment increases AMPAR subunit GluA1 S831 phosphorylation in WT cortices while decreasing S831 phosphorylation in Itgb3 KO cortices. GluA1 S831 phosphorylation promotes GluA1 targeting to post synaptic density (PSD). I concluded that αVβ3 integrin regulates AMPAR synaptic currents via mGluR5 signalling. Moreover, I speculated that, upon loss of αVβ3 integrin, mGluR5 signalling leads to increased availability of GluA1 at PSD, possibly promoting excessive excitatory transmission, which can contribute to ASD and epilepsy.Autism spectrum disorder (ASD) and epilepsy have a high degree of comorbidity. This co-occurrence is likely the result of underlying factors predisposing to both conditions. Integrins are heterodimeric receptors for extracellular matrix proteins and counter-receptors on adjacent cells. In the mouse brain, β3 integrin subunit pairs only with αV integrin subunit; loss of αV and β3 integrin subunits have been implicated in the onset of epilepsy and autism, respectively.
In this project, I investigate the effects of impairing αVβ3 integrin in the mouse cortex with the goal of identifying changes that may underlie both ASD and epilepsy, focusing on deficits in αVβ3 integrin receptor signalling at synapses.
I used AAV-mediated retrograde labelling in WT and constitutive Itgb3 KO mice to investigate the role of β3 integrin in dendritic spine number and morphology in corticopontine (CP) and commissural (COM) layer V pyramidal neurons of the medial prefrontal cortex (mPFC), two populations of pyramidal neurons that differ in terms of excitatory hodology. I found that COM neurons harboured more mushroom and fewer stubby spines compared to CP neurons in both WT and Itgb3 KO brains. Moreover, loss of β3 integrin induced a specific shortening of thin spines in CP neurons, hinting to a role of β3 integrin in immature spines.
In two different mouse models (a conditional KO for αV integrin and the constitutive KO for β3 integrin), I used comparative quantitative mass spectrometry of cortical synapses and bioinformatic protein-protein interaction (PPI) network analyses to identify genes involved in ASD and epilepsy. I found 19 proteins in common between Itgb3 and ItgaV PPI networks that were significantly changing in mass spectrometry analyses and were associated with ASD or epilepsy or both. Among these proteins, I focused of AMPA receptor (AMPAR) subunit GluA2, and group I metabotropic glutamate receptors mGluR1 and mGluR5 since they are involved in excitatory synaptic transmission.
In both mouse models, I recorded AMPAR excitatory synaptic currents in mPFC pyramidal neurons in the whole-cell patch clamp configuration upon pharmacological modulation of mGluR1/5 signalling. I isolated mGluR5 contribution using the selective antagonist MPEP in Itgb3 and ItgaV mouse models: MPEP treatment reduces AMPAR currents in both ItgaV KO and Itgb3 KO neurons. Loss of αVβ3 integrin affect selectivity mGluR5 regulation of AMPAR excitatory synaptic currents.
Since AMPAR phosphorylation affects receptor trafficking, I investigated whether mGluR5 inhibition affects AMPAR phosphorylation in cortices from WT and Itgb3 KO mice. MPEP treatment increases AMPAR subunit GluA1 S831 phosphorylation in WT cortices while decreasing S831 phosphorylation in Itgb3 KO cortices. GluA1 S831 phosphorylation promotes GluA1 targeting to post synaptic density (PSD). I concluded that αVβ3 integrin regulates AMPAR synaptic currents via mGluR5 signalling. Moreover, I speculated that, upon loss of αVβ3 integrin, mGluR5 signalling leads to increased availability of GluA1 at PSD, possibly promoting excessive excitatory transmission, which can contribute to ASD and epilepsy
Regulation of dendritic spine length in corticopontine layer V pyramidal neurons by autism risk gene β3 integrin
No full textThe relationship between autism spectrum disorder (ASD) and dendritic spine abnormalities is well known, but it is unclear whether the deficits relate to specific neuron types and brain regions most relevant to ASD. Recent genetic studies have identified a convergence of ASD risk genes in deep layer pyramidal neurons of the prefrontal cortex. Here, we use retrograde recombinant adeno-associated viruses to label specifically two major layer V pyramidal neuron types of the medial prefrontal cortex: the commissural neurons, which put the two cerebral hemispheres in direct communication, and the corticopontine neurons, which transmit information outside the cortex. We compare the basal dendritic spines on commissural and corticopontine neurons in WT and KO mice for the ASD risk gene Itgb3, which encodes for the cell adhesion molecule beta 3 integrin selectively enriched in layer V pyramidal neurons. Regardless of the genotype, corticopontine neurons had a higher ratio of stubby to mushroom spines than commissural neurons. beta 3 integrin affected selectively spine length in corticopontine neurons. Ablation of beta 3 integrin resulted in corticopontine neurons lacking long (> 2 mu m) thin dendritic spines. These findings suggest that a deficiency in beta 3 integrin expression compromises specifically immature spines on corticopontine neurons, thereby reducing the cortical territory they can sample. Because corticopontine neurons receive extensive local and long-range excitatory inputs before relaying information outside the cortex, specific alterations in dendritic spines of corticopontine neurons may compromise the computational output of the full cortex, thereby contributing to ASD pathophysiology
Dissipation and turbulence in general relativistic hydrodynamics.
No full textHydrodynamics is one of the oldest research areas in physics, with applications across all macroscopic scales in the Universe. Despite the long history of successes, however, fluid modelling still presents severe conceptual and computational challenges. Not surprisingly, the hurdles become even more formidable for relativistic flows, and new issues come to the fore too. This work is concerned with advancing multi-fluid models in General Relativity, and in particular focuses on the modelling of dissipative fluids and turbulent flows. Such models are required for an accurate description of neutron star phenomenology, and binary neutron star mergers in particular. In fact, the advent of multi-messenger astronomy—started with the first detection of a binary neutron star coalescence in 2017—offers exciting prospects for exploring the extreme physics at play during such cosmic fireworks. In this work we first focus on modelling dissipative fluids in relativity, and explore the arguably unique model that is ideally suited for describing dissipative multi-fluids in General Relativity. Modelling single fluids in relativity is already a hard task, but for neutron stars it is easy to argue that we need to understand even more complicated settings: the presence of superfluid/superconducting mixtures, for example, means that we need to go beyond single-fluid descriptions. We then consider turbulent flows and focus on how to perform “filtering” in a curved spacetime setting. We do so as most recent turbulent models in a Newtonian setting are based on the notion of spatial filtering. As the same strategy is beginning to be applied in numerical relativity, we focus on the foundational underpinnings and propose a novel scheme for carrying out filtering, ensuring consistency with the tenets of General Relativity. Finally, we discuss two applications of relevance for binary neutron star mergers. We focus on the modelling of (β-)reactions in neutron star simulations, and provide a discussion of the magnetorotational instability that is suited to highly dynamical environments like mergers. We focus on these two problems as reactions are expected to source the dominant dissipative contribution to the overall dynamics, while the magneto-rotational instability is considered crucial for sustaining the development of turbulence in mergers
Linearizing a non-linear formulation for general relativistic dissipative fluids
No full textFully non-linear equations of motion for dissipative general relativistic fluids can be obtained from an action principle involving the explicit use of lower dimensional matter spaces. More traditional strategies for incorporating dissipation-like the famous Mueller-Israel-Stewart model-are based on expansions away from equilibrium defined, in part, by the laws of thermodynamics. The goal here is to build a formalism to facilitate comparison of the action-based results with those based on the traditional approach. The first step of the process is to use the action-based approach itself to build self-consistent notions of equilibrium. Next, first-order deviations are developed directly on the matter spaces, which motivates the latter as the natural arena for the underlying thermodynamics. Finally, we identify the dissipation terms of the action-based model with first-order "thermodynamic" fluxes, on which the traditional models are built. A simple application of a single viscous fluid is considered. The description is developed in a general setting so that the formalism can be used to describe more complicated systems, for which causal and stable models are not yet available. Finally, even though our expansions are halted at first order, we sketch out how a causal response can be implemented with telegraph-type equations
A Variational Approach to Resistive General Relativistic Two-Temperature Plasmas
No full textWe develop an action principle to construct the field equations for dissipative/resistive general relativistic two-temperature plasmas, including a neutrally charged component. The total action is a combination of four pieces: an action for a multifluid/plasma system with dissipation/resistivity and entrainment; the Maxwell action for the electromagnetic field; the Coulomb action with a minimal coupling of the four-potential to the charged fluxes; and the Einstein–Hilbert action for gravity (with the metric being minimally coupled to the other action pieces). We use a pull-back formalism from spacetime to abstract matter spaces to build unconstrained variations for the neutral, positively, and negatively charged fluid species and for three associated entropy flows. The full suite of field equations is recast in the so-called “3+1” form (suitable for numerical simulations), where spacetime is broken up into a foliation of spacelike hypersurfaces and a prescribed “flow-of-time”. A previously constructed phenomenological model for the resistivity is updated to include the modified heat flow and the presence of a neutrally charged species. We impose baryon number and charge conservation as well as the Second Law of Thermodynamics in order to constrain the number of free parameters in the resistivity. Finally, we take the Newtonian limit of the “3+1” form of the field equations, which can be compared to existing non-relativistic formulations. Applications include main sequence stars, neutron star interiors, accretion disks, and the early universe
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