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.     

Direct evidence of high DNA binding activity of transcription factor AP-1 in rheumatoid arthritis synovium

Green fluorescent protein (GFP) is increasingly being used in plant biology from the cellular level to whole plant level. At the cellular level, GFP is being used as an in vivo reporter to assess frequency of transient and stable transformation. GFP has also proven to be an invaluable tool in monitoring trafficking and subcellular localization of protein. At the organ level and up, many exciting applications are rapidly emerging. The development of brighter GFP mutants with more robust folding properties has enabled better macroscopic visualization of GFP in whole leaves and plants. One interesting example has been the use of GFP to monitor virus movement in and among whole plants. GFP is also emerging as a powerful tool to monitor transgene movement and transgenic plants in the field. In a proof-of-concept study, tobacco was transformed with a modified version of the GFP gene controlled by a constitutive (35S) promoter. GFP expression in progeny plants ranged from 0% to 0.5%, and approximately 0.1% GFP was the minimal amount needed for unambiguous macroscopic detection. GFP is the first truly in vivo reporter system useful in whole plants, and we project its usefulness will increase even further as better forms of GFP genes become available.     

A case of eosinophilic pustular folliculitis (Ofuji's disease) induced by patch and challenge tests with indeloxazine hydrochloride

A 73-year-old male developed disseminated erythema over his entire body after exposure to indeloxazine hydrochloride, a cerebral activator. Patch testing with indeloxazine hydrochloride showed a positive reaction, and plaques, vesicles and pustules developed on the face after the patch test. These had the pathologic feature of eosinophilic pustular folliculitis (EPF, Ofuji's disease). A challenge test also provoked eruptions on the face, trunk, arms and legs, which were compatible with EPF. Moreover, both the patch and challenge tests with indeloxazine hydrochloride induced eosinophilia. This is the first report of drug allergy-induced EPF, where drug sensitivity induced an abnormal eosinophilic response mimicking EPF.     

The short-term effect of a smoking prevention program for the upper graders of elementary schools--the results of intervention study for two years with quasi-experimental design

The purpose of this study was to evaluate the short-term effect of a smoking prevention program for Japanese elementary school-children in the fifth and sixth grades. The program was developed with concepts found in the Know Your Body Program and the conclusions of a National Cancer Institute-convened Expert Advisory Panel, and focused on teaching about the short-term effects of smoking and on resistance to social pressures to smoke. The study was conducted with a quasi-experimental design. An intervention group (52 boys and 54 girls) received three sessions for both the fifth grade in 1992 and the sixth grade in 1993. Moreover, the intervention group received a pre-test before the first session and a post-test after the third session in each grade. A comparison group (102 boys and 91 girls) received the same tests at the same time as the intervention group, but did not receive any program on smoking prevention. The short-term effect of the program were evaluated using the results of the pre-test in the fifth grade and of the post-test in the sixth grade in both groups. The results were as follows: 1) Remarkable short-term effects of the intervention were seen in respect to awareness of the importance of not smoking in girls, and also in the knowledge of the short-term effects of smoking in both sexes. 2) The intervention was not effective with respect to intention to smoke at the age of 20 and self-efficacy of refusing to smoke in both sexes. 3) The short-term effects were not clear in the smoking behavior in both sexes because the rates of ever smokers and of monthly smokers were almost the same for two years between the intervention group and the comparison group. 4) The smoking behaviors of children, their parents and their best friends had little influence on the results of the post-test in the sixth grade.     

A 160-kDa Protein Is Essential for Hemocyanin-derived Melanosis of Prawn

ABSTRACT A purified 160-kDa protein, isolated from the cuticle of kurama prawn and named melanosis collaborating factor (MCF), was a key factor in promoting melanosis by a cooperative reaction with hemocyanin-derived phenoloxidase but hemocyanin itself was incapable of producing black pigment. The enzymatic activity of MCF in the body of the prawn was very stable against the process of freezing and thawing; the enzyme maintained more than 80% of its activity after 3 mo of storage at −2 5 °C. These results indicated that MCF, acting in conjunction with hemocyanin-derived phenoloxidase, played a crucial role in postharvest melanogenesis in prawn.     

Time-dependent deformation in an enhanced SiC/SiC composite

Time-dependent deformation in an enhanced SiC/SiC composite has been studied under constant load at high temperatures of 1200 °C, 1300 °C, and 1400 °C. Creep damage evolution was evaluated by a Young’s-modulus change of partial unloading and microscopic observation. The addition of the glassy phase in the matrix is very effective for protecting the composite from oxidation. The transient creep is dominant in creep life at all the temperatures. An empirical equation is proposed to describe creep behavior of the composite. It is found that creep activation energy increases with creep time at stresses lower than matrix cracking stress, but the activation energy remains constant at stresses higher than the matrix cracking stress. The creep strain rate of the composite is considered to be controlled by creep of fibers based on examining the time, strain, stress, and temperature dependencies of creep strain rates.     

Radiation tolerance for the SMASH-series front-end chips for a silicon micro-strip detector

The radiation tolerance for prototype front-end chips designed for a silicon micro-strip detector was examined with a ⁶⁰Co irradiation source to establish an allowable range of the radiation dose. The irradiated front-end chips were SMA²SH-64A, a 64-channel preamplifier array; SMA²SH-1, a single-channel preamplifier circuit with a comparator; and Control-C, a digital-control chip for the preamplifiers.     

Effective thermal conductivity of compressed woods

Compression is one solution to improve the strength of softwoods. The effective thermal conductivities of compressed Japanese cedars (cryptomeria japonica), which were compressed in the radial direction of the wood, were measured. Both the effective thermal conductivities in the tangential and fiber directions increase proportionally to the density increment due to the compression. However, the thermal conductivity in the radial direction (compression direction) increases slightly with the density increment. Numerical computations were conducted to explain the characteristics of thermal conductivity in the radial direction by using a microscopic heat conduction model for the compressed wood. The numerical results were compared with the measured values. And the physical mechanism of the heat conduction in the compressed woods is discussed.     

Development of a single loop EPR test method and its relation to grain boundary microchemistry for alloy 600

A single loop electrochemical potentiokinetic reactivation test method has been developed for alloy 600 that produces good passivation on all the surfaces, good etching during the reactivation scan and no appreciable pitting. It is able to quantify and discriminate between samples with a wide range of degree of sensitization. The Pa value correlates well with the minimum level of chromium in the depletion regions at the grain boundaries. It has been shown that the width of the attacked regions is much larger than the width of chromium depletion regions and it does not show any direct correlation with either depth or width or with a volume parameter of chromium depletion regions. It has been shown that the chromium carbides are not attacked during the test and that the intragranular regions attacked during the test are the sites of chromium carbides in the grain matrix. A modified Pa parameter is shown to be sensitive down to 7.5 wt% chromium in the depletion regions and indicates that the intragranular carbides have shallower depletion profiles than those at grain boundaries. Comparison of the results of the single loop and the double loop tests showed a good correlation.