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.     

A flow simulation for the epoxy casting process using a 3D finite‐element method

A three‐dimensional flow simulation for epoxy casting has been developed. A control‐volume‐based finite‐element method is employed, containing a conservative upwind formulation for the advection terms and equal order interpolations for all variables. This simulation predicts the non‐isothermal and reactive flow behavior under the gravity. The viscosity and reaction‐rate parameters were estimated by using a dynamic rheometer and a differential scanning calorimeter. The predicted flow front advancement and temperature profiles in the calculation domain similar to the mold cavity were in close agreement with the corresponding experimental results. The variation of epoxy surface configuration with flow rate also showed the same tendency between the prediction and the experiment. This simulation seems to be applicable not only to the epoxy casting, but also to other molding processes of various thermoset resins. POLYM. ENG. SCI. 45:364–374, 2005. © 2005 Society of Plastics Engineers.     

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.     

Two geometrical isomers of linoleic acid: Improved total syntheses

The total syntheses of 9(Z),12(E)- and 9(E),12(Z)-octadecadienoic acids have been carried out. A useful intermediate in both syntheses, 8-bromo-octanoic acid, recently has become available from commercial sources. This compound has been used to expedite the preparation of these isomers. The remaining carbon atoms were derived from propargyl alcohol along with either 1-heptyne or acetylene and 1-bromopentane. Because the overall yield for each sequence was roughly 15% and there were no extraordinary reaction conditions in any of the synthetic steps, the compounds could be prepared readily in multiple gram quantities. The syntheses of the two compounds were supported by data from a variety of spectroscopic techniques.     

Distribution of higher-order structures in injection-molded polypropylenes

Flexural test specimens were injection-molded from six homoisotactic polypropylenes with MFI = 0.49-25.1 dg/min under cylinder temperatures of 200-320°C. Distributions in the flow direction of higher-order structures such as crystallinity X_c, thickness of skin layer, a*-axis-oriented component fraction [A*], and crystalline orientation functions and distributions in the thickness direction of higher-order structures such as X_c, β-crystal contents, [A*], and crystalline orientation functions were studied. These higher-order structures are inhomogeneous in the flow and thickness directions, which strongly influences the product properties such as mechanical and thermal properties. Molecular orientation process in injection molding was theoretically analyzed from a viewpoint of growth of recoverable shear strain at the gate and its relaxation in the cavity, which could considerably well explain the variations in the flow and thickness directions of the quantities such as thickness of the skin layer and crystalline orientation functions which express the degree of molecular orientation.     

Continuous formation of slurry ice by cooling water–oil emulsion in a tube

Water-silicone oil emulsion with an additive, (C₂H₅O)₃SiC₃H₆NH₂, was examined as a heat storage material. A spiral tube used as a heat exchanger was immersed in a low temperature bath and the emulsion was circulated in the tube to make ice continuously. Ice was separated from the ice–liquid suspension in an outlet tank. The amount of formed ice, the temperatures of the inlet and the outlet of the heat exchanger, and the temperatures in the tube wall were measured and the overall heat transfer coefficient and the heat flux through the tube were calculated. Experiments were carried out, varying the flow rate, the temperature of cooling brine, and the thickness of tube wall. The condition under which slurry ice was formed continuously without adhesion of ice to the cooling wall was clarified. Though decrease in the thermal resistance of the tube increased the rate of ice formation or raised the brine temperature, it narrowed the range of the flow rate and of the brine temperature in which slurry ice was formed continuously.