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.     

Isolation of antimicrobial agent from the marine algae Cystoseira hakodatensis

Cystoseira hakodatensis is an unutilised brown algae belonging to family Sargassaceae. A crude methanol extract from the algae showed inhibitory effects on the growths of Bacillus cereus and Bacillus licheniformis. To isolate the major antimicrobial agent, a sequential active‐guided isolation procedure was applied: liquid–liquid extraction, column chromatography and bio‐autography. A marked antimicrobial agent (active α) was isolated in hydrophobic fraction and was determined to phenolics without carbohydrates and proteins by phytochemical test. Regarding the antimicrobial potential, the isolated active α showed better inhibitory effects against B. cereus and B. licheniformis at 2 and 4 times of lower concentrations (62.5 and 31.3 μg mL^?1) in comparison with epigallocatechin gallate. These results showed that C. hakodatensis is a potential source of antimicrobial agent capable of preventing the growth of the two bacteria.     

Models for circular data from time series spectra

Circular data are those for which the natural support is the unit circle and its toroidal extensions. Numerous constructions have been proposed which can be used to generate models for such data. We propose a new, very general, one based on the normalization of the spectra of complex-valued stationary processes. As illustrations of the new construction's application, we study models for univariate circular data obtained from the spectra of autoregressive moving average models and relate them to existing models in the literature. We also propose and investigate multivariate circular models obtained from the high-order spectra of stationary stochastic processes generated using linear filtering with an autoregressive moving average response function. A new family of distributions for a Markov process on the circle is also introduced. Results for asymptotically optimal inference for dependent observations on the circle are presented which provide a new paradigm for inference with circular models. The application of one of the new families of spectra-generated models is illustrated in an analysis of wind direction data.     

Characterization of anisotropic gas permeability and thermomechanical properties of highly textured porous alumina

Porous alumina with a highly textured microstructure was fabricated by pulse electric current sintering (PECS) using alumina platelets. Highly oriented porous alumina with a porosity of 3%–50% was obtained by a pressure-controlled method of PECS. The properties of the highly textured porous alumina were measured in two directions. The nitrogen gas permeance and thermal conductivity at room temperature were higher in the direction along the platelet length due to the higher continuity of pores and the connectivity of alumina platelets, respectively. The anisotropy of the thermal conductivity at room temperature was investigated and explained by the effect of grain size of platelets as well as morphology and orientation of pores. The bending strength was higher with the loading direction along the platelet thickness. The thermal shock strength was clearly different in the two directions. The difference in the thermal shock strength was investigated by the measurement of properties and thermal stress analysis.     

Combustion synthesis of AlN doped with carbon and oxygen

Carbon-and-oxygen-doped AlN specimens were prepared by combustion synthesis using Al, graphite, and AlN. Graphite addition changed the product color from white to blue. By XRD, the lattice constant increased slightly with increasing carbon content. Blue AlN powder was synthesized with a molar ratio of the diluent AlN of 0.2-0.5 with a fixed graphite content of 0.05. At an AlN molar ratio exceeding 0.6, carbon was not successfully incorporated due to the lower reaction temperature. Calcination at 800°C in air removed residual graphite without changing the crystal structure or product color. Oxygen, nitrogen, and carbon analyses revealed that blue AlN powders contained 0.45-0.54 mass% carbon and 1.4-1.6 mass% oxygen, while the undoped AlN contained 0.021 mass% carbon and 0.94 mass% oxygen. The origin of the white-to-blue color change was investigated via reflection measurements. Blue AlN exhibits an absorption peak at 634 nm (1.96 eV). From first-principles electronic structure calculations, the C-doped AlN and carbon-and-oxygen-doped AlN with a 1:1 ratio could be classified as p-type, whereas the O-doped AlN and 1:3 carbon-and-oxygen-doped AlN were n-type. One reason for the absorption peak at 634 nm may be a transition from the conduction band to an upper unoccupied state. These results suggest the possible control of optical and electronic properties of AlN via carbon-and-oxygen doping.     

Aqueous One-pot Synthesis of Glycopolymers by Glycosidase-catalyzed Glycomonomer Synthesis Using 4,6-Dimetoxy Triazinyl Glycoside Followed by Radical Polymerization

Glycopolymers have attracted increased attention as functional polymeric materials, and simple methods for synthesizing glycopolymers remain needed. This paper reports the aqueous one-pot and chemoenzymatic synthesis of four types of glycopolymers via two reactions: the β-galactosidase-catalyzed glycomonomer synthesis using 4,6-dimetoxy triazinyl β-D-galactopyranoside and hydroxy group-containing (meth)acrylamide and (meth)acrylate derivatives as the activated glycosyl donor substrate and as the glycomonomer precursors, respectively, followed by radical copolymerization of the resulting glycomonomer and excess glycomonomer precursor without isolating the glycomonomers. The resulting glycopolymers bearing galactose moieties exhibited specific and strong interactions with the lectin peanut agglutinin as glycoclusters.     

Role of Metabolism in Bone Development and Homeostasis

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.     

Operation of superconducting fault current limiter using vacuum interrupter driven by electromagnetic repulsion force for commutating switch

Using conventional high‐temperature superconducting wire, a model superconducting fault current limiter (SFCL) is made and tested. Solenoid coil using Bi2223 silver sheath wire is so made that inductance is as small as possible and a vacuum interrupter is connected in series to it. A conventional reactor coil is connected in parallel. When the fault current flows in this equipment, superconducting wire is quenched and current is transferred into the parallel coil because of voltage drop of superconducting wire. This large current in parallel coil actuates magnetic repulsion mechanism of vacuum interrupter. Due to opening of vacuum interrupter, the current in superconducting wire is broken. By using this equipment, current flow time in superconducting wire can be easily minimized. On the other hand, the fault current is also easily limited by large reactance of parallel coil. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 164(1): 52–61, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20315     

Active sites of Cu-ZSM-5 for the decomposition of acrylonitrile

The catalytic decomposition of acrylonitrile (AN) over Cu-ZSM-5 prepared with various Cu loadings was investigated. AN conversion, during which the nitrogen atoms in AN were mainly converted to N₂, increased as Cu loading increased. N₂ selectivities as high as 90–95% were attained. X-ray diffraction measurements (XRD) and temperature-programmed reduction by H₂ (H₂-TPR) showed the existence of bulk CuO in Cu-ZSM-5 with a Cu loading of 6.4 wt% and the existence of highly dispersed CuO in Cu-ZSM-5 with a Cu loading of 3.3 wt%. Electron spin resonance measurements revealed that Cu-ZSM-5 contains three forms of isolated Cu²⁺ ions (square-planar, square-pyramidal, and distorted square-pyramidal). The H₂-TPR results suggested that in Cu-ZSM-5 with a Cu loading of 2.9 wt% and below, Cu⁺ existed even after oxidizing pretreatment. The activity of AN decomposition over Cu/SiO₂ suggested that CuO could form N₂, but, independent of the CuO dispersion, nitrogen oxides (NO_x) were formed above 350 °C. Cu⁺ and the square-pyramidal and distorted square-pyramidal forms of Cu²⁺ showed low activity for AN decomposition. Temperature-programmed desorption of NH₃ suggested that N₂ formation from NH₃ proceeded on Cu²⁺, resulting in the formation of Cu⁺. The Cu⁺ ions were oxidized to Cu²⁺ at around 300 °C. Thus, high N₂ selectivity over Cu-ZSM-5 with a wide range of temperature was probably attained by the reaction over the square-planar Cu²⁺, which can be reversibly reduced and oxidized.     

Inhibitory effect of alpha-tocopherol on methemoglobin formation by nitric oxide in normal and acatalasemic mouse hemolysates

The inhibitory effect of alpha-tocopherol on methemoglobin formation in normal and acatalasemic mice was studied by exposing their hemolysates to nitric oxide. Methemoglobin formation in normal and acatalasemic mouse hemolysates exposed to nitric oxide were significantly inhibited by the addition of alpha-tocopherol at final concentrations ranging from 1.2 to 5.8 mM. Negative correlations were observed between the logarithm of alpha-tocopherol concentration and the methemoglobin formation. The formation of methemoglobin in acatalasemic mouse hemolysates was greater than that in normal mouse hemolysates with or without added alpha-tocopherol. The methemoglobin formation in acatalasemic mice was also significantly inhibited by addition of more than 500 units/ml of catalase, and the methemoglobin formation in normal and acatalasemic mice was also inhibited with sodium diethyldithiocarbamate at a final concentration of 1 M.