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.     

Hydrogen production through dry reforming of biogas using a porous electrochemical cell: Effects of a cobalt catalyst in the electrode and mixing of air with biogas

This paper reports the performance of porous Gd-doped ceria (GDC) electrochemical cells with Co metal in both electrodes (cell No. 1) and with Ni metal in the cathode and Co metal in the anode (cell No. 2) for CO₂ decomposition, CH₄ decomposition, and the dry reforming reaction of a biogas with CO₂ gas (CH₄ + CO₂ → 2H₂ + 2CO) or with O₂ gas in air (3CH₄ +?1.875CO₂ +?1.314O₂ → 6H₂ +?4.875CO +?0.7515O₂). GDC cell No. 1 produced H₂ gas at formation rates of 0.055 and 0.33?mL-H₂/(min?m²-electrode) per 1?mL-supplied gas/(min?m²-electrode) at 600?°C and 800?°C, respectively, by the reforming of the biogas with CO₂ gas. Similarly, cell No. 2 produced H₂ gas at formation rates of 0.40?mL-H₂/(min?m²) per 1?mL-supplied gas/(min?m²) at 800?°C from a mixture of biogas and CO₂ gas. The dry reforming of a real biogas with CO₂ or O₂ gas at 800?°C proceeded thermodynamically over the Co or Ni metal catalyst in the cathode of the porous GDC cell. Faraday's law controlled the dry reforming rate of the biogas at 600?°C in cell No. 2. This paper also clarifies the influence of carbon deposition, which originates from CH₄ pyrolysis (CH₄ → C + 2H₂) and disproportionation of CO gas (2CO → C + CO₂), on the cell performance during dry reforming. The dry reforming of a biogas with O₂ molecules from air exhibits high durability because of the oxidation of the deposited carbon by supplied air.     

Radiation detector made of a high-quality polycrystalline diamond

Radiation detector was made of a high-quality CVD polycrystalline diamond composed of frost column like structure diamond grains, and induced charge distribution spectra and drift velocities were measured by using alpha particles. As a result, the CVD polycrystalline achieved maximum induced charge of 83% of HP/HT type IIa diamond. Moreover, the CVD crystal had lower charge loss on electrons compared with the HP/HT type IIa diamond. Drift velocities of electrons and holes were v_e = 7.7 × 10⁴ and v_h = 7.3 × 10⁴cm/s at an electric field of 20 kV/cm, respectively. In addition, response function measurement for 14 MeV neutrons was carried out.     

Does mixed venous desaturation during a bed bath indicate cardiopulmonary decompensation in postoperative cardiac patients?]

The bed bath procedure consists of cleansing patients' body, passive position change, changing gown and making a bed. During the procedure, mixed venous desaturation was observed consistently in postoperative cardiac patients. We investigated the cause of the phenomenon in 22 patients undergoing cardiac surgery in their first postoperative day. The patients were breathing oxygen-enriched air via a Venturi mask. Cardiac index (CI), transluminal SvO2, arterial blood gas, Hb, DO2, VO2, FIO2, A-aDO2 and Qp/Qs were measured before and during the bed bath, while the patients were in the supine and left lateral position, respectively. Mean 8.5 +/- 1.5 minutes were required to complete the bed bath. During the bed bath, SvO2 decreased from 71 +/- 7% to 59 +/- 9% (P < 0.001), and returned to the baseline 6.5 +/- 7.4 minutes after the completion of the bed bath. VO2 increased markedly from 128 +/- 27 to 194 +/- 47 ml.min-1.m-2 (P < 0.001), while DO2 increased slightly from 480 +/- 91 to 513 +/- 110 ml.min-1.m-2 (P < 0.05). Among the determinants of DO2, CI increased slightly from 3.3 +/- 0.6 to 3.6 +/- 0.8 l.min-1.m-2, Hb remained unchanged and SaO2 decreased from 98.5 +/- 0.8 to 98.0 +/- 1.1%. FIO2 also decreased, while A-aDO2 and Qp/Qs remained unchanged. There was a negative correlation between VO2 change and SvO2 change, but no correlation between DO2 change and SvO2 change. There was a positive correlation between SaO2 change and SvO2 change, as well as between FIO2 change and SaO2 change. Therefore, the major cause of mixed venous desaturation was not the decreased DO2 or cardiopulmonary decompensation but the increased VO2 due to increased activity of the skeletal muscles. However, the decrease in SaO2 due to markedly increased O2 demand and the limited increase in CI might partially contribute to the marked decline in SvO2 through the limited increase in DO2.     

Mechanical role of reinforcement in seismic behavior of steel-strip reinforced earth wall

In the current design practices of steel-strip reinforced earth walls (SSREWs), the length of the reinforcing material is determined based on the equilibrium between the reinforcement tension and the earth pressure acting on the wall. Here, the resistance of the reinforcing material laid in the active failure zone (AFZ) is not considered. Moreover, the mechanical role of the reinforcing material against the integrity of the SSREW has not been sufficiently verified. Regarding the seismic stability of SSREW, although it is investigated by treating the entire reinforced earth wall as a rigid body, this inspection method is for gravity-retaining walls, and the difference in the seismic behavior between the SSREW and the rigid body is not clear. In this study, therefore, dynamic centrifuge model tests on 6 types of SSREWs were conducted to clarify the following items: (1) the basic earthquake behavior of a SSREW, (2) the mechanical role of the reinforcing material laid in the AFZ and (3) the mechanical role of the reinforcing material against the integrity of the SSREW. The results indicated that the reinforcing material laid in the AFZ can restrain the amount of deformation of the wall during earthquakes. Furthermore, the more stable the AFZ is, the smaller the maximum wall displacement will be.     

Synthesis of thermoresponsive block and graft copolymers via the combination of living cationic polymerization and RAFT polymerization using a vinyl ether-type RAFT agent

A novel vinyl ether-type RAFT agent, benzyl 2-(vinyloxy)ethyl carbonotrithioate (BVCT) was synthesized for various block copolymers via the combination of living cationic polymerization of vinyl ethers and reversible addition−fragmentation chain transfer (RAFT) polymerization. The novel BVCT–trifluoroacetic acid adduct play an important role to produce well-defined block copolymers, which is both as a cationogen under EtAlCl₂ initiation system in the presence of ethyl acetate for living cationic polymerization and a RAFT agent for blocks by RAFT polymerization. The resulting polymer, poly(vinyl ether)s, by living cationic polymerization had a high number average α-end functionality (≥0.9) as determined by both ¹H NMR and MALDI-TOF-MS spectrometry. In addition, this poly(vinyl ether)s worked well as a macromolecular chain transfer agent for RAFT polymerization. The RAFT polymerization of radically polymerizable monomers was conducted in toluene using 2,2′-azobis(isobutyronitrile) at 70 °C. For example, a double thermoresponsive block copolymer (MOVE₆₁-b-NIPAM₁₅₀) consisting of 2-methoxyethyl vinyl ether (MOVE) and N-isopropylacrylamide (NIPAM) was prepared via the combination of living cationic polymerization and RAFT polymerization. The block copolymer reversibly formed and deformed micellar assemblies above the phase separation temperature (T_ps) of poly(NIPAM) block in water. This BVCT is not only functioned as an initiator, but also acted as a monomer. When BVCT was copolymerized with MOVE by living cationic polymerization, followed by graft copolymerization with NIPAM via RAFT polymerization, well-defined graft copolymers (MOVE_n-co-BVCT_m)-g-NIPAM_x (n = 62–73, m = 1–9, x = 19–214) were successfully obtained. However, no micelle formed in water above T_ps of poly(NIPAM) graft chain unlike the case of block copolymers.     

Volatile aroma components and antioxidant activities of the flavedo peel extract of unripe Shiikuwasha (Citrus depressa Hayata)

The flavedo peel extracts of unripe Shiikuwasha (Citrus depressa Hayata) fruits were extracted using steam distillation (SD) or a cold-press (CP) system. Volatile aroma content and composition were determined using gas chromatography (GC) and each compound was identified using gas chromatography-mass spectrophotometry (GC-MS). The major constituents of the extracts were monoterpene hydrocarbons (91.75-93.75%[709.32-809.05 mg/100 g of fresh flavedo peel]) including limonene (43.08-45.13%[341.46-379.81 mg/100 g of fresh flavedo peel]), γ-terpinene (27.88-29.06%[219.90-245.86 mg/100 g of fresh flavedo peel]), and p-cymene (8.13-11.02%[61.47-97.22 mg/100 g of fresh flavedo peel]). The extraction process used was determined to be a decisive factor that affects the composition of key citrus aroma components, as well as the antioxidant activities of the Shiikuwasha fruit. Antioxidant capabilities of the extracts were examined by assay of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and β-carotene bleaching inhibition. The cold-press extraction system may better retain the total phenolic content of the flavedo peel and display superior antioxidant activities, compared to the steam distillation extraction method. PRACTICAL APPLICATION: Shiikuwasha (Citrus depressa Hayata) is a type of small citrus fruit, and has been used as raw material for beverage and food additive productions in Japan. It had a unique aroma composition in which the limonene content of its peels is lower than that of other commonly known citrus peels. The present study detailed the volatile aroma composition, as well as antioxidant capabilities of Shiikuwasha peel extracts of different extraction methods, that are cold-press and steam distillation methods. The results of this study may provide a basis for selection of Shiikuwasha peel extracts in food industry for citrus flavor production.     

Densification and Cell Performance of Gadolinium-Doped Ceria (GDC) Electrolyte/NiO–GDC Anode Laminates

A thin film (60 μm thick) of a gadolinium-doped ceria (GDC) electrolyte was prepared by the doctor blade method. This film was laminated with freeze-dried 42 vol% NiO–58 vol% GDC mixed powder and pressed uniaxially or isostatically under a pressure of 294 MPa. This laminate was cosintered at 1100 °–1500 °C in air for 4–12 h. The laminate warped because of the difference in the shrinkage of the electrolyte and electrode during the sintering. A higher shrinkage was measured for the electrode at 1100 °–1200 °C and for the electrolyte at 1300 °–1500 °C. The increase of the thickness of anode was effective in decreasing the warp and in increasing the density of the laminated composite. The maximum electric power density with a SrRuO₃ cathode using 3 vol% H₂O-containing H₂ fuel was 100 mW/cm² at 600 °C and 380 mW/cm² at 800 °C, respectively, for the anode-supported GDC electrolyte with 30 μm thickness.