Mechanism of membrane interaction and disruption by α-synuclein

Parkinson's disease is a common progressive neurodegenerative condition, characterized by the deposition of amyloid fibrils as Lewy bodies in the substantia nigra of affected individuals. These insoluble aggregates predominantly consist of the protein α-synuclein. There is increasing evidence suggesting that the aggregation of α-synuclein is influenced by lipid membranes and, vice versa, the membrane integrity is severely affected by the presence of bound aggregates. Here, using the surface-sensitive imaging technique supercritical angle fluorescence microscopy and F?rster resonance energy transfer, we report the direct observation of α-synuclein aggregation on supported lipid bilayers. Both the wild-type and the two mutant forms of α-synuclein studied, namely, the familiar variant A53T and the designed highly toxic variant E57K, were found to follow the same mechanism of polymerization and membrane damage. This mechanism involved the extraction of lipids from the bilayer and their clustering around growing α-synuclein aggregates. Despite all three isoforms following the same pathway, the extent of aggregation and their effect on the bilayers was seen to be variant and concentration dependent. Both A53T and E57K formed cross-β-sheet aggregates and damaged the membrane at submicromolar concentrations. The wild-type also formed aggregates in this range; however, the extent of membrane disruption was greatly reduced. The process of membrane damage could resemble part of the yet poorly understood cellular toxicity phenomenon in vivo.     

Exploring similarities in reactivity of superatom species: a combined theoretical and experimental investigation

The replacement of group 10-based materials by superatoms has gained great attention due to studies presenting similarities in electronic character and reactive nature between pairs. The current study extends the concept to systems of larger and varied composition as the pairs PdO(+) and ZrO(2)(+) as well as NiO(+) and TiO(2)(+) are interacted with C(2)H(4) and CO through DFT calculations and guided-ion-beam mass spectrometry. It is determined that the pairs readily oxidize C(2)H(4) while oxygen transfer is limited towards CO. Interestingly, within the reaction profiles for oxidation of C(2)H(4) by PdO(+) and NiO(+), a spin crossover is observed which greatly increases the exothermicity of the process. This investigation presents a major step in identifying replacements for expensive group 10 metals in catalytic materials.     

Asymptotics of the Smallest Singular Value of a Class of Toeplitz-Generated Matrices and Related Finite Rank Perturbations

Square matrices of the form X _n = T _n + f _n (T _n ^?1 )^*, where T _n is an n × n invertible banded Toeplitz matrix and f _n some positive sequence are considered. The norms of their inverses are described asymptotically as their size n increases. Certain finite rank perturbations of these matrices are shown to have no effect on this behaviour.     

Covalent connection of individualized, neutral, dendronized polymers on a solid substrate using a scanning force microscope

The synthesis of a neutral, high-molar-mass, acrylamide-based, third-generation dendronized polymer (denpol) with a defined number of azide groups at its periphery is reported. An attach-to route is used in which a first-generation denpol is reacted with second-generation (G2) dendrons. The degree of structure perfection of the resulting denpol is quantified as 99.8 %. This value was obtained after the introduction of a fluorescence label at the sites that remained unaffected by the dendronization. The high coverage was independently confirmed for the dendronization of another first-generation polymer and a closely related G2 dendron. The third-generation denpol resulting from the first dendronization experiment was spin-coated as a sub-monolayer onto highly oriented graphite precoated with an ultrathin layer of C12H25NH2, which was introduced to provide a well-defined substrate for denpol adsorption and manipulation. Scanning force microscopy revealed single denpols, which could be moved across the surface and "welded" by covalent cross-linking induced by photochemical decomposition of the azides into highly reactive nitrenes. The successful formation of covalent bonds between two denpols was confirmed by mechanically challenging the link with the scanning force microscope (SFM) tip. This is the second reported case of a move-connect-prove sequence using polymers and the SFM, which for the first time employs noncharged denpols, thus widening the applicability of this method significantly.     

Wannier-based definition of layer polarizations in perovskite superlattices

In insulators, the method of Marzari and Vanderbilt [Phys. Rev. B 56, 12 847 (1997)] can be used to generate maximally localized Wannier functions whose centers are related to the electronic polarization. In the case of layered insulators, this approach can be adapted to provide a natural definition of the local polarization associated with each layer, based on the locations of the nuclear charges and one-dimensional Wannier centers comprising each layer. Here, we use this approach to compute and analyze layer polarizations of ferroelectric perovskite superlattices, including changes in layer polarizations induced by sublattice displacements (i.e., layer-decomposed Born effective charges) and local symmetry breaking at the interfaces. The method provides a powerful tool for analyzing the polarization-related properties of complex layered oxide systems.     

On spherically convex sets and Q-matrices

Let K be a closed spherically convex subset of S^n?1 that is contained in a hemisphere, and x?(K) the radial projection onto S^n?1 of the centroid of K. Then p^Tx?(K)>0 for all p ? K. A specialization of this result to spherical simplices is used to derive a necessary condition for Q-matrices, i.e., matrices for which every corresponding linear complementarity problem has at least one solution.