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.     

Effect of Milling on Slip Casting of Partially Stabilized Zirconia

Specimens of partially stabilized zirconia were slip cast from aqueous suspensions and sintered at 1500°C for 3 h. The relative density of the cast specimens and the firing shrinkage of the sintered specimens depend on the milling time for the suspension. Vickers hardness and K_IC values of 11.46±s0.07 GN/m² and 6.10 ±0.04 MN.m^3/2, respectively, were obtained for all sintered specimens. The dispersion of the suspension is important in increasing the relative density of the cast specimens.     

A case of aneurysm of the descending thoracic aorta associated with Beh?et's disease]

A 66-year-old male with Beh?et's disease admitted again with hemoptysis. He underwent the resection and direct closure of descending aortic aneurysm 3 years ago, followed without the use of steroid. Chest CT scanning demonstrated a recurrent aneurysm of the descending aorta which was could not be detected on the previous CT only 23 days before. In the current operation, we performed resection, direct closure and wrapping of the aneurysm. The pathological examination showed a true aneurysm of Beh?et's disease. The patient is free from recurrence for 17 months since the operation under steroid therapy.     

A localized surface plasmon resonance based immunosensor for the detection of casein in milk

In this research, a localized surface plasmon resonance (LSPR) immunosensor based on gold-capped nanoparticle substrate for detecting casein, one of the most potent allergens in milk, was developed. The fabrication of the gold-capped nanoparticle substrate involved a surface-modified silica nanoparticle layer (core) on the slide glass substrate between bottom and top gold layers (shell). The absorbance peak of the gold-capped nanoparticle substrate was observed at ∼520 nm. In addition, the atomic force microscopy (AFM) images demonstrated that the nanoparticles formed a monolayer on the slide glass. After immobilizing anti-casein antibody on the surface, our device, casein immunosensor, could be applied easily for the detection of casein in the raw milk sample without a difficult pretreatment. Under the optimum conditions, the detection limit of the casein immunosensor was determined as 10 ng/mL. Our device brings several advantages to the existing LSPR-based biosensors with its easy fabrication, simple handling, low-cost, and high sensitivity.     

The Ig heavy chain gene is frequently involved in chromosomal translocations in multiple myeloma and plasma cell leukemia as detected by in situ hybridization

Chromosome rearrangement of 14q32.33 has recurrently occurred with variable partner sites, including 11q13.3, 8q24.1, 18q21.3, and 6p21.1 in multiple myeloma (MM). To assess the actual incidence of 14q32.33 translocation and to elucidate its implication in the pathogenesis of MM, we studied 42 patients with MM, plasma cell leukemia, or plasmacytoma and 5 with monoclonal gammopathy with undetermined significance (MGUS) by G-banding and molecular cytogenetic methods. Using double-color fluorescence in situ hybridization (DCFISH) with 2 Ig heavy chain (IgH) gene probes, a yeast artificial chromosome (YAC) clone containing variable region, and a phage clone containing gamma constant region, 14q32.33 translocation was detected as split signals of the IgH gene in 31 patients with plasma cell malignancies and 3 with MGUS. In contrast, of 40 patients who were assessed by G-banding, 3 (7.5%) showed the 14q+ chromosome. DCFISH detected a split of the IgH gene on interphase nuclei in 34 (73.9%) of 46 patients analyzed, whereas on metaphase spreads, it was in 22 (51.2%) of 43 patients analyzed. Interphase DCFISH was particularly useful to detect 14q32.33 translocation in 17 (65.4%) of 26 patients with normal karyotypes. Donor sites were identified in 11 of 22 patients demonstrated as carrying 14q32.33 translocation by metaphase FISH. Chromosome t(11;14)(q13.3; q32.33) was detected in 5 patients, t(8;14)(q24.1;q32.33) in 2, t(14;18)(q32.33;q21.3) in 2, and t(7;14)(q32.1;q32.33) in 1. A complex 14q32.33 translocation involving 3q and 16q24 was detected in 1 patient. Myeloma cells with t(7;14) showed myelomonocytoid surface antigen. Because rearrangements of 14q32.33 were closely associated with translocation of proto-oncogenes into the IgH gene, our findings indicate that 14q32.33 translocation with various partner chromosomes is a critical event in the pathogenesis of MM and MGUS.     

A novel technique for a DC brushless motor without position sensors

A dc brushless motor is a kind of synchronous motor driven by an inverter and requires sensors to detect the rotor position. As one of the methods, the induced voltages of a brushless motor have been utilized in practice. However, there are some problems in this method, e.g., the motor can obtain insufficient torque due to the low induced voltages in a low-speed range. This paper proposes a new method which controls the inverter angular frequency ω₁ by using inherent characteristics wherein the torque current i_r is almost proportional to the internal phase angle φ where the primary flux of a synchronous motor is controlled to be constant. If the parameters of a motor are given exactly, the speed regulation is quite small and the transient characteristics with high response and high starting torque are obtained. Furthermore, it is possible to operate a synchronous motor in the field-weakening range. Here, the principle of the control method and the performance characteristics of a dc brushless motor having no position sensors are discussed. The simulation and the experimental results of the tested machine show that the proposed method is very useful for practical applications.     

Adaptive covariate acquisition for minimizing total cost of classification

Machine Learning - In some applications, acquiring covariates comes at a cost which is not negligible. For example in the medical domain, in order to classify whether a patient has diabetes or not,...     

Synthesis and electronic property of platinum nanowire and nanoparticle in mesoporous silica template

Platinum nanowires and nanoparticles were selectively synthesized in mesoporous silicas FSM-16 and HMM-1. The nanowires are 3 nm in diameter and several hundred nm to μm in length with high crystallinity. Pt nanowires and nanoparticles can be isolated by dissolving silica matrix with HF. The Pt wires extracted from organosilica HMM-1 have a nanonecklace structure, while the wires from siliceous FSM-16 have a nanorod structure. The extracted Pt nanoparticles (3 nm in size) on HOPG show the Coulomb staircase phenomena in STM/STS analysis. The mechanism for formation of the Pt nanowires is based on the migration of Pt ions in the mesoporous channels.