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.     

Effect of light source spectral modulation on wavelength interrogation in fiber Bragg grating sensors and its reduction

In the fiber Bragg grating sensing using a superluminescent diode as the light source and an arrayed waveguide grating as the wavelength interrogator, the wavelength measurement error due to the spectral modulation of the superluminescent diode is theoretically formulated and quantitatively analyzed by computer simulation. It is shown that the wavelength measurement errors produced with the use of real superluminescent diodes are in very good agreement with the theoretical results. In order to reduce the wavelength measurement error due to the spectral modulation of superluminescent diode, two different types of remedies are proposed that utilize the temperature switching of superluminescent diode and that adjust the bandwidths of fiber Bragg grating and arrayed waveguide grating, and their efficacies are experimentally demonstrated together with good quantitative agreement with the theoretical calculation.     

Analysis of brushless three-phase synchronous generator without exciter

Recently, a demand for small-capacity generators has been increasing as electric sources in small ships and automobiles or as portable electric sources driven by engines. It is desired that the structure of small-capacity generators be simple and robust, and that the generators be highly reliable, easily maintained and controlled. This paper describes an analysis of the original brushless synchronous generator without exciter. The output voltage can be adjusted in the wide range by controlling the stator dc current. To analyze the characteristics of this generator, the finite element method is applied. It is found that the results of theoretical analysis agree well with the experimental results.     

Pulse-Width Dependence in Current-Driven Magnetization Reversal Using GaMnAs-Based Double-Barrier Magnetic Tunnel Junction

We have investigated the current pulse width dependence on current-driven magnetization reversal in double-barrier structures using GaMnAs-based magnetic tunneling junctions (MTJ) in order to clarify the origin of low threshold current density for current-driven magnetization reversal. Comparing with the case of single-barrier MTJ, the pulse-width dependence reveals that threshold current density is reduced by double-barrier MTJ. We confirmed that the threshold current density in the order of 10⁴ A/cm² is estimated considering the effect of current pulse width.     

Silica removal from Mokai, New Zealand, geothermal brine by treatment with lime and a cationic precipitant

Preliminary experiments using two chemicals (CaO, a quicklime, and a cationic nitrogen-bearing precipitant, EC-004) to remove silica from geothermal brine were undertaken at the Mokai geothermal plant, New Zealand. The brine was mixed with the reagent (CaO or EC-004). The reaction was studied from the start of the experiment (NRT, 0 min, no retaining time) and after 15 min (15RT) at 90 °C. The concentration of silica in the brine was initially 954 mg/l, and decreased linearly with increasing reagent concentration. When CaO is added, the silica concentration at 15RT was 200 mg/l lower than at NRT and became almost zero on addition of 1.5 g/l. In contrast, when EC-004 is added, the total silica concentration nearly reaches the solubility of amorphous silica at 90 °C. In order to prevent silica scaling in Mokai brines cooled to 90 °C, the CaO and EC-004 added should be individually adjusted to 0.5 g/l and 80 mg/l, respectively.     

Suppression of adjuvant arthritis in rats by oral administration of type II collagen in combination with type I interferon

Foliar application of cytozyme to 30-day-old black-gram plants resulted 48% increase of dry matter accumulation. The increase in fresh and dry weights of total plants was largely due to enhanced CO2 assimilation rates which were associated with increased RuBP carboxylase activities. The photochemical characteristics in the isolated chloroplasts exhibited an increase of 32, 28 and 40%, measured as the photoreduction of DCPIP, FeCN and NADP, respectively. Cytozyme treatment also resulted an increase in the chlorophyll content in leaves.     

Steady-state torque control system with secondary-current feedback for three-phase squirrel-cage induction motors

This paper presents a highly stable steady-state torque control system with a feedback of a secondary current signal. The torque control system is constructed with a feedback of the secondary current (I₂) signal using a quick response magnetic-field sensor constructed with an amorphous core multivibrator bridge, which can solve the secondary resistance change problem for temperature variation in the IM. Moreover, we added a state feedback to the system to improve the response speed for the unit step function of a torque order. The I₂ sensor method has advantages especially at a low-speed range, in which conventional method using an integrator shows control errors.     

An image analyzing system using an artificial neural network forevaluating the parenchymal echo pattern of cirrhotic liver and chronichepatitis

To objectively evaluate the parenchymal echo pattern of cirrhotic liver and chronic hepatitis, the authors applied an image analyzing system (IAS) using a neural network. Autopsy specimens in a water tank (n=13) were used to examine the relationship between the diameter of the regenerative nodule and the coarse score (CS) calculated by IAS. CS was significantly correlated with the diameter of the regenerative nodule (p<0.0001, r=0.966). CS is considered to be useful for evaluating the coarseness of the parenchymal echo pattern     

Molecular basis of a hereditary type I protein S deficiency caused by a substitution of Cys for Arg474

The molecular basis for a hereditary type I protein S (PS) deficiency was investigated. DNA sequence analysis in the proband showed a novel missense mutation substituting Cys (TGT) for Arg474 (CGT) that is a highly conserved amino acid residue among the related proteins. This missense mutation cosegregated with the type I PS deficiency in this family. Transient expression studies showed that the secretion of the recombinant Cys-mutant PS was markedly decreased compared with that of the recombinant wild-type PS, reproducing the observed phenotype of type I deficiency. Stable expression and pulse-chase experiments demonstrated an intracellular degradation and an impaired secretion of the recombinant Cys-mutant PS. Furthermore, the substitution of Arg474 by Ala or Glu, but not by Lys, markedly reduced the secretion of the recombinant PS mutants in transient expression studies, suggesting that a positively charged basic amino acid might be needed at residue 474 and might play a key role in the protein structure and conformation of the sex hormone binding globulin-homology domain of the PS molecule. We postulate that the loss of the highly conserved Arg474 might be responsible for the type I PS deficiency inherited in this family.