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.     

Enhancement of nutraceutical properties of licorice callus cultures using sample pre-treatment strategy

Licorice is an herbal plant in the Leguminosae family, and its roots and rhizomes are used as sweeteners in food and confectionery products. Moreover, it has a distinct inflammatory activity. In the present study, a sample pre-treatment method to induce the deglycosylation of active metabolites in callus cultures of Glycyrrhiza inflata (GI) and Glycyrrhiza glabra (GG) was developed. The results of the method evaluation showed the biotransformation of ononin to formononetin, a rare flavonoid found in trace amounts in licorice. The magnitude of enhancement was 3- and 19-fold in the GI and GG samples, respectively. Moreover, the anti-inflammatory activity assay showed that the potency of the sample pre-treatment group was higher than that of the untreated group because it exerted an enhanced suppression of cyclo-oxygenase 2 (COX-2), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) gene expression. This is the first report on the anti-inflammatory activity of licorice callus, which has the potential to be utilised as a functional food for health promotion. These findings support the idea of using sample preparation to impart nutraceutical properties to plant products.     

Dielectric relaxation of vegetable-based polyurethane

Vegetable-based polyurethane (PU) was prepared in the thin film form by spin coating. This polymer is synthesised from castor oil, which can be extracted from the seeds of a native plant in Brazil called mamona. This polymer is biocompatible and is being used as material for artificial bone. The PU was characterised by dielectric spectroscopy in a wide range of frequency (10^–5 Hz to 10⁵ Hz) and by thermally stimulated discharge current (TSDC) measurements. The glass transition temperature (T _g = 39°C) was determined and using the initial rise method the activation energy was found to be 1.58 eV.     

High-gain hybrid amplifier consisting of cascaded fluoride-based TDFA and silica-based EDFA in 1458-1540 nm wavelength region

A hybrid optical fibre amplifier is described that consists of a fluoride-based thulium-doped fibre amplifier and a silica-based erbium-doped fibre amplifier connected in a cascade. The amplifier has a gain of more than 25 dB and a noise figure of less than 9 dB over a wide wavelength region of 1458-1540 nm.     

Correlation between serum levels of alanine aminotransferase and ferritin in male blood donors with antibody to hepatitis C virus

Chronic hepatitis C has been demonstrated to be associated with hepatic iron overload, and the hypothesis that the disease activity of hepatitis C is associated with iron cytotoxicity was tested in male volunteer blood donors. Sera with either antibody to hepatitis C virus or hepatitis B surface antigen were selected for determination of ferritin concentration and alanine aminotransferase activity. A correlation between serum ferritin concentration (Y; microgram/l) and alanine aminotransferase activity (X; IU/l) was found in donors with antibody to hepatitis C (log Y = 0.65 x log X + 0.98, r = 0.53, and P < 0.01). The correlation was lower in donors with hepatitis B surface antigen (r = 0.37; P < 0.01). Hepatitis C virus infection probably induces time-dependent iron accumulation associated with the progression of disease activity, while hepatitis B virus infection results in a variety of iron loads with different clinical features. The high disease activity related to hyperferritinemia suggests the presence of iron-induced liver damage in donors with hepatitis C.     

Unperturbed dimension of poly(4-acetoxystyrene) measured in good and theta solvents

In order to obtain the additional data concerning the unperturbed dimension of poly-4-substituted styrene, light scattering measurements are performed on the twenty-two fractions with molecular weight of (0.91–352)·10⁴ of poly(4-acetoxystyrene) in dioxan at 25°C, from which the molecular weight obtained was found easily to be evaluated with the gel permeation chromatography using THF. Phase separation experiments for this polymer indicate that the theta state is attained in isopropyl acetate at 19.7°C and butyl acetate at 26.8°C. By making viscosity measurements at that state, the value of K_Θ is directly evaluated as 5.4·10^?4 dl g^?1. The limiting viscosity number is also obtained in good solvents, THF and dioxan, at 25°C and constants of the Mark-Houwink-Sakurada equation in each solvent are determined. Further, approximately the same K_Θ as above is obtained from these data with the Stockmayer-Fixman plot. The calculated value of steric factor, 2.37, on this polymer may be plausible, compared with those of polyvinylaromatic derivatives.     

Novel T-rail electrodes for substrate removed low-voltage high-speed GaAs/AlGaAs electrooptic modulators

A novel traveling-wave electrode utilizing capacitively loaded T-rail elements was developed for low-voltage high-speed substrate-removed GaAs/AlGaAs electrooptic modulators. Electrodes with varying dimensions were fabricated and characterized. Electrode phase velocity, characteristic impedance, loss coefficient, and capacitive loading were extracted from the measured s-parameters up to 40 GHz. Electrode was also simulated using a finite-element solver. The measured and calculated electrode capacitance values were found to be in excellent agreement, showing that the electrode can be precisely designed. Approaches were outlined to provide a group velocity-matched very high-speed modulator electrode suitable for a low drive-voltage substrate-removed GaAs/AlGaAs electro-optic modulator