The Role Of Α-Synuclein In Brain Lipid Metabolism And Inflammation

Alpha-synuclein (Snca) is a small cytosolic protein that is ubiquitously expressed in the nervous system and comprises 0.5-1% of all cytosolic protein, but its biological function is poorly understood. Although Snca function has been studied in lipid metabolism, the function of Snca in brain lipid metabolism under inflammatory conditions is yet to be elucidated. We utilized several model systems including primary cultured astrocytes and microglia, Snca deficient and mutant knock-in mice, and a radiolabeled free fatty acid steady state-kinetic mouse model to determine Snca role in neuroinflammation. Herein, we have determined several major roles of Snca during inflammation: (i) dBcAMP treatment increases 20:4n-6 uptake in astrocytes and this increase appears to be due to increased expression of long chain acyl-CoA synthetases 3 and -4 coupled with a reduction in acyl-CoA hydrolase expression in the presence of reduced Snca expression. (ii) Snca deficient mice have higher basal brain 2-arachidonyl glycerol (2-AG) levels compared to wildtype and lipopolysaccharide (LPS) stimulation further exacerbated 2-AG synthesis.(iii) In primary microglia, LPS-treatment reduced released 2-AG into medium concomitantly with reduced Snca expression and Snca deficient microglia had a delayed response to LPS stimuli. This supports the hypothesis that Snca expression is linked to 2-AG release in primary microglia and may contribute to regulating the phagocytic phenotype.(iv) Using Snca gene-ablated mice, we determined the impact of Snca on brain 20:4n-6 metabolism during LPS-induced inflammatory response in vivo using an established steady-state kinetic model. In Snca deficient mouse brain, 20:4n-6 uptake was significantly increased 1.3-fold. In the organic fraction, tracer entering into Snca deficient mouse total brain phospholipids was significantly increased 1.4-fold, accounted for by increased incorporation into choline glycerophospholipids and phosphatidylinositol. In the neutral lipid fraction, 20:4n-6 incorporation into diacylglycerol of Snca deficient mice was significantly reduced by 75%. Hence, under inflammatory conditions where 20:4n-6 release is enhanced, Snca has a crucial role in modulating 20:4n-6 metabolism, and the absence of Snca results in increased uptake and incorporation into lipid pools associated with enhanced lipid-mediated signaling during neuroinflammatory response. Herein, we focus on the role of Snca in downstream eicosanoid biosynthesis, inflammatory mediators, and lipid signaling molecules linking Snca to inflammatory response elucidating a key step in neuroinflammation

Proposal for manipulating and detecting spin and orbital states of trapped electrons on helium using cavity quantum electrodynamics

We propose to couple an on-chip high finesse superconducting cavity to the lateral-motion and spin state of a single electron trapped on the surface of superfluid helium. We estimate the motional coherence times to exceed 15 microseconds, while energy will be coherently exchanged with the cavity photons in less than 10 nanoseconds for charge states and faster than 1 microsecond for spin states, making the system attractive for quantum information processing and cavity quantum electrodynamics experiments. Strong interaction with cavity photons will provide the means for both nondestructive readout and coupling of distant electrons.Comment: 4 pages, 3 figures, supplemental material

Theory for nucleation at an interface and magnetization reversal of a two-layer nanowire

Nucleation at the interface between two adjoining regions with dissimilar physical properties is investigated using a model for magnetization reversal of a two-layer ferromagnetic nanowire. Each layer of the nanowire is considered to have a different degree of magnetic anisotropy, representing a hard magnetic layer exchange-coupled to a softer layer. A magnetic field applied along the easy axis causes the softer layer to reverse, forming a domain wall close to the interface. For small applied fields this state is metastable and complete reversal of the nanowire takes place via activation over a barrier. A reversal mechanism involving nucleation at an interface is proposed, whereby a domain wall changes in width as it passes from the soft layer to the hard layer during activation. Langer’s statistical theory for the decay of a metastable state is used to derive rates of magnetization reversal, and simple formulas are found in limiting cases for the activation energy, rate of reversal, and critical field at which the metastable state becomes unstable. These formulas depend on the anisotropy difference between each layer, and the behavior of the reversal rate prefactor is interpreted in terms of activation entropy and domain-wall dynamics

055— Ketogenic Diet and Dendritic Morphology in a Mouse Model of Repetitive Behavior

Repetitive motor behaviors are invariant movements with no apparent function. They are associated with several disorders, including autism spectrum disorders (ASD). However, little is known about the causes of these restricted behavior patterns, and effective treatments are lacking. ASD has recently been treated with a ketogenic diet (KD). Now a popular fad, KD is a high-fat, low-carb diet that has treated intractable epilepsy for decades. However, the mechanisms mediating KD’s beneficial effects are still unclear. We first show KD can attenuate repetitive circling behavior. We then assessed dendritic spine density in the left and right dorsolateral striatum as a potential explanation of the reduction of repetitive behavior with KD. Dendritic spine density is a good indicator of the number of synapses in a region, having implications for synaptic transmission. We imaged the striatum as previous research suggests basal ganglia circuitry is impaired in the development of repetitive behavior. Golgi-Cox histochemistry was performed in order to view dendritic spines and dendritic branching patterns. Dendrite length and the number of spines were measured and used to calculate dendritic spine density for each hemisphere. Hemispheric lateralization of dendritic spine density was also explored for an association with the preferred direction of circling

Query processing of spatial objects: Complexity versus Redundancy

The management of complex spatial objects in applications, such as geography and cartography, imposes stringent new requirements on spatial database systems, in particular on efficient query processing. As shown before, the performance of spatial query processing can be improved by decomposing complex spatial objects into simple components. Up to now, only decomposition techniques generating a linear number of very simple components, e.g. triangles or trapezoids, have been considered. In this paper, we will investigate the natural trade-off between the complexity of the components and the redundancy, i.e. the number of components, with respect to its effect on efficient query processing. In particular, we present two new decomposition methods generating a better balance between the complexity and the number of components than previously known techniques. We compare these new decomposition methods to the traditional undecomposed representation as well as to the well-known decomposition into convex polygons with respect to their performance in spatial query processing. This comparison points out that for a wide range of query selectivity the new decomposition techniques clearly outperform both the undecomposed representation and the convex decomposition method. More important than the absolute gain in performance by a factor of up to an order of magnitude is the robust performance of our new decomposition techniques over the whole range of query selectivity

Point force manipulation and activated dynamics of polymers adsorbed on structured substrates

We study the activated motion of adsorbed polymers which are driven over a structured substrate by a localized point force.Our theory applies to experiments with single polymers using, for example, tips of scanning force microscopes to drag the polymer.We consider both flexible and semiflexible polymers,and the lateral surface structure is represented by double-well or periodic potentials. The dynamics is governed by kink-like excitations for which we calculate shapes, energies, and critical point forces. Thermally activated motion proceeds by the nucleation of a kink-antikink pair at the point where the force is applied and subsequent diffusive separation of kink and antikink. In the stationary state of the driven polymer, the collective kink dynamics can be described by an one-dimensional symmetric simple exclusion process.Comment: 7 pages, 2 Figure

Variation bounds for spherical averages

We consider variation operators for the family of spherical means, with special emphasis on $L^p\to L^q$ estimatesMTM2017-82160-C2-1-P RYC2018-025477-I Ikerbasqu