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.     

Characterization of pigmented granules in minocycline-induced cutaneous pigmentation: observations using fluorescence microscopy and high-performance liquid chromatography

Ambiguous abdominal situs, asplenia/polysplenia and severe cardiac malformations characterize heterotaxy in humans. These anomalies result from the inability of the developing embryo to establish normal left-right asymmetry. We have studied an interesting family in which the heterotaxy phenotype segregates as an X-linked recessive trait. In order to map the heterotaxy locus (HTX), we have analysed 39 family members using highly-polymorphic microsatellite markers from the X chromosome. One of these markers, DXS994, shows no recombination with the disease locus in 20 informative meioses. Linkage analysis results in a maximum lod score of 6.37. Current genetic and physical mapping data assign the order of loci in Xq24-q27.1 as cen-DXS1001-(DXS994, HTX)-DXS984-tel. These results establish the first mapping assignment of situs abnormalities in humans.     

Epidermodysplasia verruciformis accompanied by familial large granular lymphocytosis and a decrease in T lymphocytes

A 40-year-old man with epidermodysplasia verruciformis showed a decrease in peripheral blood T cells and abnormal expansion of large granular lymphocytes, accompanied by increased natural killer cell activity. Surface marker analysis of his large granular lymphocytes demonstrated that the subset, CD 57+ and CD 16+, had increased. His father, who had no skin lesions of epidermodysplasia verruciformis, displayed similar blood changes and his brother showed a decrease in T cells and a slight increase in CD 16+ natural killer cells, whereas his mother revealed only a slight decrease in T cells. Our present study indicates that epidermodysplasia verruciformis might be associated with hereditary abnormal expansion of large granular lymphocytes and a decrease in T cells.     

A 10-s doping technology for the application of low-temperaturepolysilicon TFTs to giant microelectronics

A bucket-type high-density (0.25-1.2-mA/cm²) low-energy (500-2000 V) ion source was utilized for high-speed phosphorus doping directly into a thin polysilicon layer without cap SiO₂. Doping gas with He dilution was selected to reduce etching of polysilicon film. Excimer laser (XeCl, 8 mm×8 mm) pulse annealing was introduced to activate effectively the doped impurity. The combination of these techniques provided a practically low sheet resistance for the TFT source, drain, and gate with a short time doping. The low-temperature polysilicon TFT fabricated with a doping time of 10 s had characteristics comparable to those of that fabricated by a longer time doping or conventional ion implantation, showing the practicality of this technology and its promise for giant microelectronics     

Superconductivity in W-containing diamond-like nanocomposite films

Superconductivity in a tungsten-containing carbon-oxide film was reported. The film with 500 nm thickness was deposited onto polycrystalline silicon oxides using chemical vapor deposition and the co-sputtering of a tungsten metal target. The bonding state of the carbon atoms and the macroscopic and microscopic crystal structure of the film were investigated by Raman spectroscopy, X-ray diffraction and transmission electron microscopy measurements. From the experimental results, we determined that this film essentially had an amorphous structure. The temperature dependence on resistivity was measured in the temperature range of 2–300 K. Resistive superconducting transition was observed at 3.8 K. The dc magnetizations were measured in the temperature range of 1.8–6.5 K. The diamagnetism resulting from a superconductive state was observed below 3.75 K, which is consistent with a resistive superconducting transition. It is thought that the finite sized clusters of the different superconductive transition temperatures cooperatively produce a macroscopic superconducting phenomenon.     

Cognitive model of team cooperation in en-route air traffic control

Since controller teams are in charge of en-route air traffic control, team cooperation is a key issue for good control performance. We conducted ethnographic field observation at the Tokyo Area Control Center and then analyzed the obtained data to develop a cognitive model of team cooperation in en-route air traffic control. We segmented conversational records, behavioral records, and so on by control unit, and then clarified relations between the segments and identified expert knowledge and judgment behind them. Cognitive processes of controller teams were reconstructed based on a concept of distributed cognition. The analysis revealed that the mutual belief model is applicable to team cooperation processes, the role assignment of tasks within a controller team is implicit and that control plans are implemented smoothly once team situation awareness has been established. A cognitive model of controllers?? team cooperation has been constructed based on these findings.     

Characterization of highly active silver catalyst for NOx reduction in lean-burning engine exhaust

A new Ag/Al₂O₃ catalyst for removing NOx in lean exhaust gas was developed. Oxidized Ag/Al₂O₃ catalyst is highly active for reduction of NOx with ethanol and propene, whereas reduced Ag/Al₂O₃ catalyst is less active for these reactions. Selectivity to N₂ is also high on the oxidized Ag/Al₂O₃ compared to that on the reduced Ag/Al₂O₃. XRD and SEM studies of these two types of Ag catalysts suggest that oxidation induces an interaction between Ag and the support, where the particles are grown in large size. In contrast, the metallic Ag particles are finely dispersed by the reduction process. Although dispersion of Ag particles is decreased by the oxidation process, the catalytic activity is increased. This suggests that the Ag-alumina sites created in the high temperature oxidizing environment are active in catalytic reduction of NOx. This revised version was published online in July 2006 with corrections to the Cover Date.     

Repeatedly foldable AMOLED display

In this study, a 5.9‐inch foldable active‐matrix organic light emitting diode (AMOLED) display was developed. A folding test was performed repeatedly. The display survived the folding test (100,000 folds) with a curvature radius of 2 mm. To protect an organic light emitting diode (OLED) against moisture, inorganic passivation layers are provided on the upper and lower sides of the flexible display. Using our transfer technology, high density passivation layers can be obtained. The measured water vapor transmission rate of the layer is 7 × 10^?6 g/m²?day or less, which improves OLED reliability. With these techniques, we have developed a book‐type display, which is repeatedly foldable like a book, and a tri‐fold display including a display area, which is foldable in three.     

Bacteriological, pharmacokinetic and clinical evaluation of azithromycin in the pediatric field]

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluation in the pediatric patients. Antibacterial activity of AZM against 43 clinical isolates: AZM exhibited slightly lower activity against Gram-positive bacteria and 2-8-fold higher activity against Gram-negative bacteria than erythromycin or clarithromycin. Plasma or urine samples were collected from eight patients receiving the drug in fine granular form, and two patients receiving it in capsules for the determination of drug levels. The elimination half-lives of AZM after administration at dose of 10 mg/kg/day for 3 days were 50.0 and 51.2 hours for fine granules, and 41.5 hours for capsules. AUC0-infinity was 11.7 and 24.3 micrograms.hr/ml for fine granules, and 8.3 micrograms.hr/ml for capsules. The cumulative excretion rates up to 120 hours after the start of treatment were 8.24 and 13.84% for fine granules, and 3.83% for capsules. AZM was administered to 123 patients once daily at 3.7-20.0 mg/kg body weight over 3 to 5 days with reference to the standard dose of 10 mg/kg. The drug was used to treat patients with pharyngitis, tonsillitis, scarlet fever, pneumonia, mycoplasmal pneumonia, chlamydial pneumonia, otitis media, pertussis, intestinal infection, and SSTI. The effectiveness of AZM was evaluated in 109 cases. The drug was rated "excellent" in 65.1% of the patients and "good" in 29.4%, resulting in an efficacy rate of 94.5%. Furthermore, AZM eradicated 43 of 46 (93.5%) bacteria that had been identified before the treatment. Three patients complained of side effects of urticaria (1 case) and diarrhea (2 cases). Abnormal laboratory changes were reported as follows: decreased leukocyte (3 cases), increased eosinophil (5), increased platelet (2), increased eosinophil and platelet, elevated GPT (1), and elevated GOT and GPT (1). The abnormalities, however, were mild enough to raise no clinically significant problems. In conclusion, AZM in once daily regimen was effective and safe in treatment of pediatric infections.