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.     

An analysis of shielding against DC magnetic fields generated by electric railways. Evaluation of effective permeability of fine structure

This paper describes an effective analysis of magnetic shielding based on homogenization. The analyses become time‐consuming if the problems include the magnetic substances having fine structure. The homogenization of the structure makes it possible to analyze effectively the magnetic fields. The authors introduce a method to estimate the effective permeability of the homogenized substance. This method can be applied to any periodic structure made of magnetic substance. The magnetic shielding effects by the structures against direct‐current (DC) fields generated by electric railways are analyzed by using the present method. As a result, it is found that the overhead way and the protective fence near the railway work as a magnetic shield, whose effects can be improved by appropriate arrangement of those constructions. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 160(4): 7–15, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20310     

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.     

An investigation of water-gas transport processes in the gas-diffusion-layer of a PEM fuel cell by a multiphase multiple-relaxation-time lattice Boltzmann model

In order to study water-gas transport processes in the gas-diffusion-layer (GDL) of a proton exchange membrane (PEM) fuel cell system, a multiphase, multiple-relaxation-time lattice Boltzmann model is presented in this work. The model is based on the mean-field diffuse interface theory and can handle the multiphase flows with large density ratios and various viscosities. By using the standard bounce back boundary condition and an approximate average scheme for the non-slip and wetting boundary walls, respectively, detailed liquid-gas transportation in the GDL, in which exact boundary condition is difficult to be implemented, can be simulated. Unlike most of lattice Boltzmann methods based on the Bhatnagar–Gross–Krook collision operator, the present model shows a viscosity-independent velocity field, which is very important in simulating multiphase flows where various viscosities coexist. We validate our model by simulating a static droplet on a wetting wall and compare with theoretical predictions. Then, we simulate a water-gas flow in the GDL of a PEM fuel cell and investigate the saturation-dependent transport properties under different conditions. The results are shown to be qualitatively consistent with the previous numerical and theoretical works.     

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.     

Further studies on elastic-plastic stable fracture utilizing the T integral

Herein, the T^* fracture parameter is shown to have relevance to the mechanics of elastic-plastic fracture. Specifically, it is shown to have certain advantages over the currently established plastic fracture parameters such as J and CTOA. Finite element analyses of experimental data were carried out as a means to obtain a comparison of the effectiveness of the plastic fracture parameters. T^* is clearly superior. A note on problems associated with satisfying the plastic incompressibility constraint is also included.