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.     

Dynamic probe of ZnTe(110) surface by scanning tunneling microscopy

The reconstructed surface structure of the II–VI semiconductor ZnTe (110), which is a promising material in the research field of semiconductor spintronics, was studied by scanning tunneling microscopy/spectroscopy (STM/STS). First, the surface states formed by reconstruction by the charge transfer of dangling bond electrons from cationic Zn to anionic Te atoms, which are similar to those of IV and III–V semiconductors, were confirmed in real space. Secondly, oscillation in tunneling current between binary states, which is considered to reflect a conformational change in the topmost Zn–Te structure between the reconstructed and bulk-like ideal structures, was directly observed by STM. Third, using the technique of charge injection, a surface atomic structure was successfully fabricated, suggesting the possibility of atomic-scale manipulation of this widely applicable surface of ZnTe.     

Supramolecular Zn(II)-Dipicolylamine-Azobenzene-Aminocyclodextrin-ATP Complex: Design and ATP Recognition in Water

Cyclodextrins (CyDs) are water-soluble host molecules possessing a nanosized hydrophobic cavity. In the realm of molecular recognition, this cavity is used not only as a recognition site but also as a reaction medium, where a hydrophobic sensor recognizes a guest molecule. Based on the latter concept, we have designed a novel supramolecular sensing system composed of Zn(II)-dipicolylamine metal complex-based azobenzene (1-Zn) and 3A-amino-3A-deoxy-(2AS,3AS)-γ-cyclodextrin (3-NH₂-γ-CyD) for sensing adenosine-5′-triphosphate (ATP). 1-Zn showed redshifts in the UV-Vis spectra and induced circular dichroism (ICD) only when both ATP and 3-NH₂-γ-CyD were present. Calculations of equilibrium constants indicated that the amino group of 3-NH₂-γ-CyD was involved in the formation of supramolecular 1-Zn/3-NH₂-γ-CyD/ATP. The Job plot of the ICD spectral response revealed that the stoichiometry of 1-Zn/3-NH₂-γ-CyD/ATP was 2:1:1. The pH effect was examined and 1-Zn/3-NH₂-γ-CyD/ATP was most stable in the neutral condition. The NOESY spectrum suggested the localization of 1-Zn in the 3-NH₂-γ-CyD cavity. Based on the obtained results, the metal coordination interaction of 1-Zn and the electrostatic interaction of 3-NH₂-γ-CyD were found to take place for ATP recognition. The “reaction medium approach” enabled us to develop a supramolecular sensing system that undergoes multi-point interactions in water. This study is the first step in the design of a selective sensing system based on a good understanding of supramolecular structures.     

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.     

Gas Effusion Spectra of Fullerenes

Gas effusion spectra of fullerenes are studied. Three peaks of toluene are found in gas effusion spectra dp/dT-T. Two peaks of oxygen are found in gas effusion spectra dN/dt-T of samples kept in the air after annealing to avoid the toluene. These phenomena confirmed to be reversible are discussed by treating fullerenes as intercalated materials.