Interferon-γ acutely augments inhibition of neocortical layer 5 pyramidal neurons

BACKGROUND: Interferon-γ (IFN-γ, a type II IFN) is present in the central nervous system (CNS) under various conditions. Evidence is emerging that, in addition to its immunological role, IFN-γ modulates neuronal morphology, function, and development in several brain regions. Previously, we have shown that raising levels of IFN-β (a type I IFN) lead to increased neuronal excitability of neocortical layer 5 pyramidal neurons. Because of shared non-canonical signaling pathways of both cytokines, we hypothesized a similar neocortical role of acutely applied IFN-γ. METHODS: We used semi-quantitative RT-PCR, immunoblotting, and immunohistochemistry to analyze neuronal expression of IFN-γ receptors and performed whole-cell patch-clamp recordings in layer 5 pyramidal neurons to investigate sub- and suprathreshold excitability, properties of hyperpolarization-activated cyclic nucleotide-gated current (Ih), and inhibitory neurotransmission under the influence of acutely applied IFN-γ. RESULTS: We show that IFN-γ receptors are present in the membrane of rat's neocortical layer 5 pyramidal neurons. As expected from this and the putative overlap in IFN type I and II alternative signaling pathways, IFN-γ diminished Ih, mirroring the effect of type I IFNs, suggesting a likewise activation of protein kinase C (PKC). In contrast, IFN-γ did neither alter subthreshold nor suprathreshold neuronal excitability, pointing to augmented inhibitory transmission by IFN-γ. Indeed, IFN-γ increased electrically evoked inhibitory postsynaptic currents (IPSCs) on neocortical layer 5 pyramidal neurons. Furthermore, amplitudes of spontaneous IPSCs and miniature IPSCs were elevated by IFN-γ, whereas their frequency remained unchanged. CONCLUSIONS: The expression of IFN-γ receptors on layer 5 neocortical pyramidal neurons together with the acute augmentation of inhibition in the neocortex by direct application of IFN-γ highlights an additional interaction between the CNS and immune system. Our results strengthen our understanding of the role of IFN-γ in neocortical neurotransmission and emphasize its impact beyond its immunological properties, particularly in the pathogenesis of neuropsychiatric disorders

Effect of tool coatings on surface grain refinement in orthogonal cutting of AISI 4140 steel

Recrystallization mechanisms leading to the generation of ultrafine grains (UFG) by surface severe plastic deformation (S2PD) at low temperatures (< 0.5Tm (melting temperature)) have been investigated over the last years. Material removal processes like broaching impose large plastic strains along the shear plane during chip formation, leading in many cases to changes in the workpiece subsurface microstructure. In this work the influence of the cutting material on surface grain recrystallization were studied on broaching of AISI 4140q&t steel. Orthogonal cutting tests were carried out in dry conditions on a broaching machine using tools with different coatings. Uncoated cemented carbide inserts were geometrically prepared using fixed abrasive grinding processes and then coated by physical vapor deposition (PVD) with Al2O3 and CrVN thin films. Workpiece subsurface layers were analyzed after machining by Focused Ion Beam (FIB-SEM) and X-ray diffraction (XRD). The presented results show the influence of the cutting material on the final microstructure of the machined workpieces through the determination of the final grain sizes and dislocation densities

Products, coproducts and singular value decomposition

Products and coproducts may be recognized as morphisms in a monoidal tensor category of vector spaces. To gain invariant data of these morphisms, we can use singular value decomposition which attaches singular values, ie generalized eigenvalues, to these maps. We show, for the case of Grassmann and Clifford products, that twist maps significantly alter these data reducing degeneracies. Since non group like coproducts give rise to non classical behavior of the algebra of functions, ie make them noncommutative, we hope to be able to learn more about such geometries. Remarkably the coproduct for positive singular values of eigenvectors in $A$ yields directly corresponding eigenvectors in A\otimes A.Comment: 17 pages, three eps-figure

Explicit modeling of volatile organic compounds partitioning in the atmospheric aqueous phase

The gas phase oxidation of organic species is a multigenerational process involving a large number of secondary compounds. Most secondary organic species are water-soluble multifunctional oxygenated molecules. The fully explicit chemical mechanism GECKO-A (Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere) is used to describe the oxidation of organics in the gas phase and their mass transfer to the aqueous phase. The oxidation of three hydrocarbons of atmospheric interest (isoprene, octane and α-pinene) is investigated for various NOx conditions. The simulated oxidative trajectories are examined in a new two dimensional space defined by the mean oxidation state and the solubility. The amount of dissolved organic matter was found to be very low (yield less than 2% on carbon atom basis) under a water content typical of deliquescent aerosols. For cloud water content, 50% (isoprene oxidation) to 70% (octane oxidation) of the carbon atoms are found in the aqueous phase after the removal of the parent hydrocarbons for low NOx conditions. For high NOx conditions, this ratio is only 5% in the isoprene oxidation case, but remains large for α-pinene and octane oxidation cases (40% and 60%, respectively). Although the model does not yet include chemical reactions in the aqueous phase, much of this dissolved organic matter should be processed in cloud drops and modify both oxidation rates and the speciation of organic species

Explicit modeling of volatile organic compounds partitioning in the atmospheric aqueous phase

The gas phase oxidation of organic species is a multigenerational process involving a large number of secondary compounds. Most secondary organic species are water-soluble multifunctional oxygenated molecules. The fully explicit chemical mechanism GECKO-A (Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere) is used to describe the oxidation of organics in the gas phase and their mass transfer to the aqueous phase. The oxidation of three hydrocarbons of atmospheric interest (isoprene, octane and α-pinene) is investigated for various NOx conditions. The simulated oxidative trajectories are examined in a new two dimensional space defined by the mean oxidation state and the solubility. The amount of dissolved organic matter was found to be very low (yield less than 2% on carbon atom basis) under a water content typical of deliquescent aerosols. For cloud water content, 50% (isoprene oxidation) to 70% (octane oxidation) of the carbon atoms are found in the aqueous phase after the removal of the parent hydrocarbons for low NOx conditions. For high NOx conditions, this ratio is only 5% in the isoprene oxidation case, but remains large for α-pinene and octane oxidation cases (40% and 60%, respectively). Although the model does not yet include chemical reactions in the aqueous phase, much of this dissolved organic matter should be processed in cloud drops and modify both oxidation rates and the speciation of organic species

Statistical properties of genealogical trees

We analyse the statistical properties of genealogical trees in a neutral model of a closed population with sexual reproduction and non-overlapping generations. By reconstructing the genealogy of an individual from the population evolution, we measure the distribution of ancestors appearing more than once in a given tree. After a transient time, the probability of repetition follows, up to a rescaling, a stationary distribution which we calculate both numerically and analytically. This distribution exhibits a universal shape with a non-trivial power law which can be understood by an exact, though simple, renormalization calculation. Some real data on human genealogy illustrate the problem, which is relevant to the study of the real degree of diversity in closed interbreeding communities.Comment: Accepted for publication in Phys. Rev. Let

A quark model analysis of the charge symmetry breaking in nuclear force

In order to investigate the charge symmetry breaking (CSB) in the short range part of the nuclear force, we calculate the difference of the masses of the neutron and the proton, $\Delta {\rm M}$, the difference of the scattering lengths of the p-p and n-n scatterings, $\Delta a$, and the difference of the analyzing power of the proton and the neutron in the n-p scattering, $\Delta A(\theta)$, by a quark model. In the present model the sources of CSB are the mass difference of the up and down quarks and the electromagnetic interaction. We investigate how much each of them contributes to $\Delta {\rm M}$, $\Delta a$ and $\Delta A(\theta)$. It is found that the contribution of CSB of the short range part in the nuclear force is large enough to explain the observed $\Delta A(\theta)$, while $\Delta a$ is rather underestimated.Comment: 26 pages,6 figure

Systematic expression analysis of plasticity-related genes in mouse brain development brings PRG4 into play

Background: Plasticity-related genes (Prgs/PRGs) or lipid phosphate phosphatase-related proteins (LPPRs) comprise five known members, which have been linked to neuronal differentiation processes, such as neurite outgrowth, axonal branching, or dendritic spine formation. PRGs are highly brain-specific and belong to the lipid phosphate phosphatases (LPPs) superfamily, which influence lipid metabolism by dephosphorylation of bioactive lipids. PRGs, however, do not possess enzymatic activity, but modify lipid metabolism in a way that is still under investigation. Results: We analyzed mRNA expression levels of all Prgs during mouse brain development, in the hippocampus, neocortex, olfactory bulbs, and cerebellum. We found different spatio-temporal expression patterns for each of the Prgs, and identified a high expression of the uncharacterized Prg4 throughout brain development. Unlike its close family members PRG3 and PRG5, PRG4 did not induce filopodial outgrowth in non-neuronal cell lines, and does not localize to the plasma membrane of filopodia. Conclusion: We showed PRG4 to be highly expressed in the developing and the adult brain, suggesting that it is of vital importance for normal brain function. Despite its similarities to other family members, it seems not to be involved in changes of cell morphology; instead, it is more likely to be associated with intracellular signaling

Plasticity-Related Gene 5 Is Expressed in a Late Phase of Neurodifferentiation After Neuronal Cell-Fate Determination

During adult neurogenesis, neuronal stem cells differentiate into mature neurons that are functionally integrated into the existing network. One hallmark during the late phase of this neurodifferentiation process is the formation of dendritic spines. These morphological specialized structures form the basis of most excitatory synapses in the brain, and are essential for neuronal communication. Additionally, dendritic spines are affected in neurological disorders, such as Alzheimer's disease or schizophrenia. However, the mechanisms underlying spinogenesis, as well as spine pathologies, are poorly understood. Plasticity-related Gene 5 (PRG5), a neuronal transmembrane protein, has previously been linked to spinogenesis in vitro. Here, we analyze endogenous expression of the PRG5 protein in different mouse brain areas, as well as on a subcellular level. We found that native PRG5 is expressed dendritically, and in high abundance in areas characterized by their regenerative capacity, such as the hippocampus and the olfactory bulb. During adult neurogenesis, PRG5 is specifically expressed in a late phase after neuronal cell-fate determination associated with dendritic spine formation. On a subcellular level, we found PRG5 not to be localized at the postsynaptic density, but at the base of the synapse. In addition, we showed that PRG5-induced formation of membrane protrusions is independent from neuronal activity, supporting a possible role in the morphology and stabilization of spines