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.     

Critical heat flux on a flat plate heater located at the middle of a duct in forced flow of pressurized He II

Critical heat fluxes (CHFs) were measured for two types of rectangular ducts containing horizontal flat plate heaters. One has the flat plate heater of 6 mm wide and 20 mm long located on the inner lower wall at 50 mm from the inlet. The other duct has two horizontal flat plates of 6 mm wide and 20 mm long on inner upper and lower walls at 50 mm from the inlet. The equation of CHF for the forced convection containing a new nondimensional-parameter m introduced in order to calculate cross-sectionally averaged liquid temperature at the center of the duct was derived based on two fluid model, ordinary convection theorem and experimental results. It was confirmed that this correlation can describe not only the author's data on the duct but also other worker's data for channels with different shapes and sizes.     

Rapid detection cytomegalovirus pneumonia in recipients of bone marrow transplant: evaluation and comparison of five survey methods for bronchoalveolar lavage fluid

To detect cytomegalovirus-associated interstitial pneumonia (CMV-IP) in recipients of BMT in its earliest stage, five CMV methods were assessed for their usefulness using bronchoalveolar lavage fluid as the test specimen. Of the 43 cases enrolled in the study, PCR was positive in 12 cases, shell vial in eight, culture in eight and cytology in three. There were no positive cases in in situ hybridization. Based on this result, the 43 cases were classified into four groups: Group 1, three cases: positive in PCR, shell vial and cytology; Group 2, five cases: positive in PCR and shell vial; Group 3, four cases: positive only in PCR; and Group 4, 31 cases: negative in all CMV tests. Cases in Group 1 were judged as having the highest risk of overt CMV-IP. They were successfully treated with a combination of ganciclovir and immunoglobulin. Group 2 was diagnosed as having active CMV infection and ganciclovir monotherapy was effective for these patients. Groups 3 and 4 were not given anti-CMV therapy, but they were free from CMV-related manifestations throughout the study. The sensitivity and specificity of each survey method for the detection of Groups 1 and 2 were 1.0 and 0.89 in PCR, 1.0 and 1.0 in shell vial, 0.88 and 1.0 in culture, and 0.38 and 1.0 in cytology. Similarly, the positive and negative predictive values were 0.67 and 1.0 in PCR, 1.0 and 1.0 in shell vial, 1.0 and 0.97 in culture, and 1.0 and 0.88 in cytology. Thus, CMV survey on bronchoalveolar fluid was thought to be useful in detecting post BMT CMV-IP in its earliest stage.     

Hepatitis GB virus C genome in the serum of aplastic anaemia patients receiving frequent blood transfusions

GB virus C (GBV-C) RNA was detected in five of 18 patients with aplastic anaemia who had received blood transfusions, whereas it was not detected in eight patients who had not received any transfusions. Antibody against hepatitis C virus (anti-HCV) was detected in nine patients in the transfusion group, compared with one of eight who had not received any transfusions. Therefore, the route of transmission of both GBV-C and HCV in these patients appeared to have been multiple blood transfusion. Since all of the GBV-C RNA-positive patients harboured anti-HCV, GBV-C seems to frequently superinfect with HCV. Neither GBV-C nor HCV is likely to have been a causative agent of the anaemia in the cases examined.     

Westernized food habits and concentrations of serum lipids in the Japanese

It has recently been reported that there exists a new 'RING-finger' protein family among the zinc-finger (Zf) proteins. Previously, we had isolated the mouse Mel-18 cDNA (mMel-18) encoding the nuclear RING-finger protein that exhibits an ability to bind to a nonspecific DNA column. Here, we have isolated and characterized the human Mel-18 cDNA (hMel-18) using the mMel-18 cDNA as a probe. The deduced hMel-18 protein contains 344 amino acids (38 kDa) with a RING-finger motif, a helix-loop-helix (HLH)-like structure and a Pro/Ser-rich region. The hMel-18 gene is conserved among vertebrates. Its mRNA is highly expressed in placenta, lung and kidney, but the level is low in liver, pancreas and skeletal muscle. Using in situ hybridization, we mapped hMel-18 to band q22 of chromosome 12. It is possible that the Mel-18/bmi-1 gene family represents a mammalian homologue of the Drosophila polycomb gene group.     

A light-transmitting two-dimensional photodetector array using a-Sipin photodiodes and poly-Si TFT's integrated on a transparent substrate

A light-transmitting two-dimensional photodetector array (32×32 cells) using amorphous silicon (a-Si) pin photodiodes and polysilicon (poly-Si) thin film transistors (TFT's) integrated on a transparent substrate has been developed for use in a free-space optical switching network. The fabrication and the characteristics of the photodetector array are discussed. With driving circuits and sensing amplifiers, this photodetector array shows a minimum detectable power of -25 dBm and an insertion loss of 0.4 dB for an incident optical beam with a diameter of 550 μm. By monitoring the positions and the states of input optical beams, this photodetector array can be used to control the optical paths in photonic switching systems, such as a 1024-input-port optical concentrator     

Heat transfer and flow of He II in narrow channels

Heat transfer and fluid flow of He II in a long, narrow channel connected to a bath that supplies a constant supply of heat have been investigated by numerical simulations by using the simplified model of Kitamura et al. [Cryogenics 37 (1) (1997) 1]. Such channels are used to cool compact, stable, low-temperature magnets. The fluid flow is driven by natural convection and the mutual friction between the normal fluid and the superfluid.In this model, the thermomechanical effect and the Goter-Mellink mutual friction balance each other. A consequence of this balance is that the velocity and temperature distributions of He II can be characterized by a dimensionless, dependent parameter equal to the ratio of the fluid speeds of internal convection to the total fluid flow. After a sudden application of heat flux, the internal convection dominates over the total fluid flow until the establishment of steady-state temperature gradients. This predicts that the time required to set up the steady-state total fluid flow is proportional to the total heat capacity in the channel.     

Normal uterus and FIGO stage I endometrial carcinoma: dynamic gadolinium-enhanced MR imaging

Dynamic magnetic resonance (MR) imaging was performed on a 1.5-T superconducting unit for evaluation of 26 stage I endometrial carcinomas. To establish the appearance of the normal uterus, 27 normal uteri were also evaluated. After rapid injection of gadopentetate dimeglumine, dynamic images were obtained every 30 seconds with the spin-echo technique in the sagittal plane. On dynamic studies of endometrial carcinoma, the tumor-myometrial contrast was marked at 120 seconds after administration of gadopentetate dimeglumine (contrast-to-noise ratio [C/N], 26.0). The tumor-myometrial contrast on the dynamic study was more marked than that on postcontrast T1-weighted images (C/N, 10.0) and on T2-weighted images (C/N, 2.14). Dynamic and postcontrast MR images were superior in enabling differentiation of viable tumors from necrosis or residual secretion in the endometrial cavity. In the evaluation of presence of tumor and myometrial invasion, the accuracy of T2-weighted imaging and dynamic imaging was 67.9% and 84.9%, respectively.