Lipid peroxidation is essential for α-synuclein-induced cell death.

Parkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated α-synuclein (α-Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric α-Syn on one of the major markers of oxidative stress, lipid peroxidation, in primary co-cultures of neurons and astrocytes. We found that oligomeric but not monomeric α-Syn significantly increases the rate of production of reactive oxygen species, subsequently inducing lipid peroxidation in both neurons and astrocytes. Pre-incubation of cells with isotope-reinforced polyunsaturated fatty acids (D-PUFAs) completely prevented the effect of oligomeric α-Syn on lipid peroxidation. Inhibition of lipid peroxidation with D-PUFAs further protected cells from cell death induced by oligomeric α-Syn. Thus, lipid peroxidation induced by misfolding of α-Syn may play an important role in the cellular mechanism of neuronal cell loss in Parkinson's disease. We have found that aggregated α-synuclein-induced production of reactive oxygen species (ROS) that subsequently stimulates lipid peroxidation and cell death in neurons and astrocytes. Specific inhibition of lipid peroxidation by incubation with reinforced polyunsaturated fatty acids (D-PUFAs) completely prevented the effect of α-synuclein on lipid peroxidation and cell death

Dynamic model of gene regulation for the lac operon

Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution

Generalized Heisenberg Algebras and Fibonacci Series

We have constructed a Heisenberg-type algebra generated by the Hamiltonian, the step operators and an auxiliar operator. This algebra describes quantum systems having eigenvalues of the Hamiltonian depending on the eigenvalues of the two previous levels. This happens, for example, for systems having the energy spectrum given by Fibonacci sequence. Moreover, the algebraic structure depends on two functions f(x) and g(x). When these two functions are linear we classify, analysing the stability of the fixed points of the functions, the possible representations for this algebra.Comment: 24 pages, 2 figures, subfigure.st

Phase operators, temporally stable phase states, mutually unbiased bases and exactly solvable quantum systems

We introduce a one-parameter generalized oscillator algebra A(k) (that covers the case of the harmonic oscillator algebra) and discuss its finite- and infinite-dimensional representations according to the sign of the parameter k. We define an (Hamiltonian) operator associated with A(k) and examine the degeneracies of its spectrum. For the finite (when k < 0) and the infinite (when k > 0 or = 0) representations of A(k), we construct the associated phase operators and build temporally stable phase states as eigenstates of the phase operators. To overcome the difficulties related to the phase operator in the infinite-dimensional case and to avoid the degeneracy problem for the finite-dimensional case, we introduce a truncation procedure which generalizes the one used by Pegg and Barnett for the harmonic oscillator. This yields a truncated generalized oscillator algebra A(k,s), where s denotes the truncation order. We construct two types of temporally stable states for A(k,s) (as eigenstates of a phase operator and as eigenstates of a polynomial in the generators of A(k,s)). Two applications are considered in this article. The first concerns physical realizations of A(k) and A(k,s) in the context of one-dimensional quantum systems with finite (Morse system) or infinite (Poeschl-Teller system) discrete spectra. The second deals with mutually unbiased bases used in quantum information.Comment: Accepted for publication in Journal of Physics A: Mathematical and Theoretical as a pape

Distribution of moisture in reconstructed oil paintings on canvas during absorption and drying: a neutron radiography and NMR study

Moisture is a driving factor in the long-term mechanical deterioration of canvas paintings, as well as for a number of physico–chemical degradation processes. Since the 1990s a number of publications have addressed the equilibrium hygroscopic uptake and the hygro-mechanical deformation of linen canvas, oil paint, animal glue, and ground paint. In order to visualise and quantify the dynamic behaviour of these materials combined in a painting mock-up or reconstruction, we have performed custom-designed experiments with neutron radiography and nuclear magnetic resonance (NMR) imaging. This paper reports how both techniques were used to obtain spatially and temporally resolved information on moisture content, during alternate exposure to high and low relative humidity, or in contact with liquids of varying water activities. We observed how the canvas, which is the dominant component in terms of volumetric moisture uptake, absorbs and dries rapidly, and, due to its low vapour resistance, allows for vapour transfer towards the ground layer. Moisture desorption was generally found to be faster than absorption. The presence of sizing glue leads to a local increase of moisture content. It was observed that lining a painting with an extra canvas results in a damping effect: i.e. absorption and drying are significantly slowed down. The results obtained by NMR are complementary to neutron radiography in that they allow accurate monitoring of water ingress in contact with a liquid reservoir. Quantitative results are in good agreement with adsorption isotherms. The findings can be used for risk analysis of paintings exposed to changing micro-climates or subjected to conservation treatments using water. Future studies addressing moisture-driven deformation of paintings can make use of the proposed experimental techniques

Mitochondrial dysfunction in Parkinsonian mesenchymal stem cells impairs differentiation

Sporadic cases account for 90-95% of all patients with Parkinson's Disease (PD). Atypical Parkinsonism comprises approximately 20% of all patients with parkinsonism. Progressive Supranuclear Palsy (PSP) belongs to the atypical parkinsonian diseases and is histopathologically classified as a tauopathy. Here, we report that mesenchymal stem cells (MSCs) derived from the bone marrow of patients with PSP exhibit mitochondrial dysfunction in the form of decreased membrane potential and inhibited NADH-dependent respiration. Furthermore, mitochondrial dysfunction in PSP-MSCs led to a significant increase in mitochondrial ROS generation and oxidative stress, which resulted in decrease of major cellular antioxidant GSH. Additionally, higher basal rate of mitochondrial degradation and lower levels of biogenesis were found in PSP-MSCs, together leading to a reduction in mitochondrial mass. This phenotype was biologically relevant to MSC stemness properties, as it heavily impaired their differentiation into adipocytes, which mostly rely on mitochondrial metabolism for their bioenergetic demand. The defect in adipogenic differentiation was detected as a significant impairment of intracellular lipid droplet formation in PSP-MSCs. This result was corroborated at the transcriptional level by a significant reduction of PPARγ and FABP4 expression, two key genes involved in the adipogenic molecular network. Our findings in PSP-MSCs provide new insights into the etiology of 'idiopathic' parkinsonism, and confirm that mitochondrial dysfunction is important to the development of parkinsonism, independent of the type of the cell

Raman study of self-assembled InAs/InP quantum wire stacks with varying spacer thickness

Self-assembled InAs/InP (001) quantum wire stacks have been investigated by means of Raman scattering. The characteristics of the observed vibrational modes show clear evidence of confinement and atomic intermixing between As and P atoms from the wire and the spacer. The change in the intermixing with spacer layer thickness and growth temperature is investigated. Likewise, the effect of annealing on the exchange of As and P atoms is also studied. Resonance effects in confined and interface phonons are discussed for excitation in the vicinity of the InAs E1 critical point. Finally, the energy of the interface modes is related to the structural characteristics of the wires by comparing the experimental data with a lattice dynamic calculation based on the dielectric continuum [email protected] [email protected] [email protected]

Quaternary geology, geomorphology and tectonics in the Ogosta river valley system, the Danubian plain (Bulgaria)

The Quaternary in the Ogosta River valley system (the Danubian plain) is represented by various genetic types of continental Quaternary sediments (eolian, alluvial, deluvial, proluvial). They lie on a diverse pre-Quaternary base. It is uneven and with various denudation. The accepted correlation schemes are based on local data in which the tectonic factor and duration of deformation have not been accounted for. The present work considers the complex results obtained during the investigation of the Quaternary sediments and formations. The filling consists of clayey-sandy or calcareous-sandy materials, coloured in rusty nuances by iron hydroxides. Their age has been determined on the basis of the found fauna: Elephas meridionalis Nesti,Anancus arvernensis Cr. et Gob (Bakalov, Nikolov, 1962)

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria