A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Broadband bowtie belt nanoantennas

In this article, we study a linear array of bowtie nanoantennas placed between two metallic strips that can work from 800 to 1420 nm (600 nm linewidth), with an electric field enhancement factor close to 20. We study the dynamical change of the position of the electric field enhancement amongst different elements in the array and, at the same time, the effects of dispersion on the scalability of the array elements. A systematic analysis and methodology to produce an array that can operate over a large bandwidth whilst maintaining the electric field enhancement without significant variation is provided.     

Oxidation of doped europium in BaMgAl10O17 by annealing studied by x‐ray‐absorption fine‐structure measurements

Abstract— We studied the influence of annealing in air on doped europium in BaMgAl₁₀O₁₇ by performing x‐ray absorption fine‐structure measurements. We determined the oxidation of doped divalent europium by annealing in air at over 500°C. The interatomic distance between the europium and the surrounding oxygen atoms was compressed by oxidation. It also appears that the oxidation process of europium is determined by the diffusion of oxygen into BaMgAl₁₀O₁₇.     

Protection against adoptive transfer of autoimmune diabetes mediated through very late antigen-4 integrin

The very late antigen-4 (VLA-4) integrin expressed on the surface of lymphocytes and macrophages can regulate their migration to inflammatory sites as well as control cellular activation. The role of VLA-4 in the establishment of autoimmune diabetes is not easily predicted given the multiplicity of adhesion pathways and their differential use by various cell types. The contribution of VLA-4 to insulin-dependent diabetes mellitus was investigated by administration of VLA-4-specific monoclonal antibodies (MoAb) in an adoptive transfer model of disease in NOD mice. This study shows that VLA-4-specific MoAbs profoundly inhibit the development of diabetes with protection sustained by repeated MoAb exposure. Insulitis was completely inhibited during treatment and progressed to a severe degree once MoAb treatment was suspended, yet approximately 40% of treated recipients failed to become diabetic during 1-2 months post-treatment. Although we cannot rule out depletion of a relatively minor subpopulation of cells by prolonged anti-VLA-4 MoAb exposure, this inhibition of diabetes onset by treatment with MoAbs to VLA-4 supports a dependence on VLA-4 for cellular functions leading to diabetes and demonstrates that a significant disease modifying effect can be mediated by targeting the VLA-4 integrin.     

Schottky barrier heights of contact metals to p-type ZnSe

Schottky barrier heights (SBHs) of a variety of metals (In, Cd, Nb, Ti, W, Cu, Ag, Au, Ni, Pt, and Se) contacting to p-ZnSe grown by a molecular beam epitaxy method were determined by analyzing capacitance-voltage (C-V) and/or current density-voltage (J-V) curves. The SBH values of the Au and Ni contacts were determined from intersections of straight lines of the C⁻²-V curves to be 1.23 and 1.13 eV, respectively. The J-V calculations provided a large SBH value of 1.2 ± 0.1 eV for a variety of metals, indicating that the Fermi-level could be pinned at the contact interface. Reduction of the SBH values to a level lower than 0.4 eV and/or increase of doping concentrations to a level higher than 10²⁰ cm⁻³ are essential to obtain an ohmic contact with contact resistivity of around 10⁻³ Ω·cm².     

High performance liquid chromatographic separation of stereoisomeric bile acids as their UV-sensitive esters

High performance liquid chromatographic separation of a series of mono-, di- and trihydroxylated 5β-cholanic acids which differ only in position and configuration of hydroxyl groups at positions C-3, C-7 and/or C-12, is reported. The C-24 free acids were derivatized to four different classes of UV-sensitive esters, i.e.,p-bromophenacyl (BP),m-methoxyphenacyl (MP), 4-nitrophthalimidemethyl (NPM) and 9-anthrylmethyl (AM) esters, and chromatographed on two, variants of C₁₈ reversed-phase columns (Nova-Pak C₁₈ and Zorbax ODS) with methanol-water systems as mobile phase. Separation efficiency and elution order of some isomeric pairs were influenced by both the structure of the C-24 ester groups and the nature of the columns used. Excellent chromatographic properties were found for those derivatives, particularly for the NPM esters.