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.     

Preparation of Mn2+-Cu+ co-doped P2O5–ZnO–Al2O3 glasses and their red fluorescence properties

To make a Mn²⁺-doped red glass phosphor that can be excited with ultraviolet (UV) light of light-emitting diodes (LEDs), 60P₂O₅-35ZnO-5Al₂O₃-8MnO-xCu₂O glasses (x = 0-1.00) were prepared by a melt-quenching method at 1200-1400°C for 30-180 minutes in atmospheric air, and the redox of Mn and Cu as well as fluorescence properties were investigated. The Mn²⁺ ion was not reduced and oxidized in the melting, quenching, and annealing processes. The valence of Cu in the glasses changed in the order of 0, 1+, and 2+ with the increase in the amount of Cu₂O and in the melting temperature and time. In this study, a 60P₂O₅-35ZnO-5Al₂O₃-8MnO-0.10Cu₂O glass melted at 1250°C for 90 minutes, having the highest Cu⁺ concentration, showed the strongest Mn²⁺ red fluorescence under the UV light at 275 nm. This strong Mn²⁺ red fluorescence has been caused by the energy transfer from excited Cu⁺ ions to Mn²⁺ ions.     

High-gain hybrid amplifier consisting of cascaded fluoride-based TDFA and silica-based EDFA in 1458-1540 nm wavelength region

A hybrid optical fibre amplifier is described that consists of a fluoride-based thulium-doped fibre amplifier and a silica-based erbium-doped fibre amplifier connected in a cascade. The amplifier has a gain of more than 25 dB and a noise figure of less than 9 dB over a wide wavelength region of 1458-1540 nm.     

Surgical treatment for primary cardiac malignant lymphoma

A 60-year-old woman who complained of palpitation was diagnosed as ventricular tachycardia on electrocardiography and admitted to our hospital. The ultrasonic cardiography showed cardiac tumor in right ventricle and right atrium. Due to the obstruction of the right ventricle inflow by the tumor, we immediately performed resection of cardiac tumor and repair of right ventricle wall under cardiopulmonary bypass. The tumor was diagnosed as malignant lymphoma by pathological examination for surgical specimen of tumor. After operation her general condition was good, but residual cardiac lymphoma developed large size. We performed radiation therapy for cardiac lymphoma. Therefore the lymphoma was reduced to minimum size. Six months after operation metastatic malignant lymphoma appeared at whole body. So we performed chemotherapy for reduction of systemic malignant lymphoma. At first the chemotherapy was very effective. But metastasis spread rapidly and effectiveness of chemotherapy reduced. Thirteen months after operation she died for respiratory distress, probably due to metastatic brain tumor.     

Unperturbed dimension of poly(4-acetoxystyrene) measured in good and theta solvents

In order to obtain the additional data concerning the unperturbed dimension of poly-4-substituted styrene, light scattering measurements are performed on the twenty-two fractions with molecular weight of (0.91–352)·10⁴ of poly(4-acetoxystyrene) in dioxan at 25°C, from which the molecular weight obtained was found easily to be evaluated with the gel permeation chromatography using THF. Phase separation experiments for this polymer indicate that the theta state is attained in isopropyl acetate at 19.7°C and butyl acetate at 26.8°C. By making viscosity measurements at that state, the value of K_Θ is directly evaluated as 5.4·10^?4 dl g^?1. The limiting viscosity number is also obtained in good solvents, THF and dioxan, at 25°C and constants of the Mark-Houwink-Sakurada equation in each solvent are determined. Further, approximately the same K_Θ as above is obtained from these data with the Stockmayer-Fixman plot. The calculated value of steric factor, 2.37, on this polymer may be plausible, compared with those of polyvinylaromatic derivatives.     

Ionic transport in amorphous anodic titania stabilised by incorporation of silicon species

Incorporation of silicon species from an alloy substrate into anodic titania is shown to stabilise the structure of the film, facilitating investigation of the ionic transport processes in amorphous titania grown at high efficiency. Thus, an amorphous anodic film developed on a sputtering-deposited Ti-6 at.%Si alloy formed to 100 V in phosphoric acid electrolyte in contrast to a partially crystalline film developed on relatively pure titanium at <20 V. Silicon species, which are immobile and act as marker species in the growing film, are present in the inner 58% of the film thickness. Evidently, the film material forms simultaneously at the film/electrolyte and alloy/film interfaces by co-operative transport of cations and anions, as is usual in amorphous anodic oxides. The phosphate anions incorporated from the electrolyte migrate inward at 0.34 times the rate of O²⁻ ions and hence are present in the outer 62% of the film thickness.     

Efficiency of repeated batch penicillin fermentation using two fermentors. Computer simulation and optimisation

Repeated batch operation using two fermentors (RBTF) to penicillin fermentation was demonstrated by computer simulation to improve productivity. Three operation modes were compared: chemostat, repeated batch operation using a single fermentor (RBSF) and RBTF; in each case account was made of the lag period before growth. The simulated fermentor performances were assessed on the basis of the penicillin productivity and concentration; the simulation was based on published batch fermentation data. It was shown that RBTF was superior to RBSF and chemostat. The advantage of RBTF increased as the lag period became greater.