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.     

Photoinduced Formation of Small Gold Particles in Silica Gels

AuCl⁻₄ ions in sol-gel-derived silica gels (Au/silica gels) were photoreduced by ultraviolet light irradiation at room temperature. In the presence of ethylene glycol in the silica gels, small Au particles were effectively formed by the irradiation. When the storage temperature of the gels was increased in the dark after the irradiation, the surface plas-mon resonance absorption peak of the Au particles was shifted to longer wavelengths, indicating that the Au particles became large. At a storage temperature below 9°C, Au particles could not be observed in the silica gels. The apparent activation energy of Au particle formation was estimated to be 17. 3 kcal·tmol⁻¹.     

Photoluminescence and doping mechanism of theranostic Eu3+/Fe3+ dual-doped hydroxyapatite nanoparticles

Theranostic nanoparticles currently have been regarded as an emerging concept of ‘personalized medicine’ with diagnostic and therapeutic dual-functions. Eu³⁺ doped hydroxyapatite (HAp) has been regarded as a promising fluorescent probe for in vivo imaging applications. Additionally, substitution of Ca²⁺ with Fe³⁺ in HAp crystal may endow the capability of producing heat upon exposure to a magnetic field. Here we report a preliminary study of doping mechanism and photoluminescence of Eu³⁺ and Fe³⁺ doped HAp nanoparticles (Eu/Fe:HAp). HAp with varied concentration of Eu³⁺ and Fe³⁺ doping are presented as Eu(10 mol%):HAp, Eu(7 mol%)-Fe(3 mol%):HAp, Eu(5 mol%)-Fe(5 mol%):HAp, Eu(3 mol%)-Fe(7 mol%):HAp, and Fe(10 mol%):HAp in the study. The results showed that the HAp particles, in nano-size with rod-like morphology, were successfully doped with Eu³⁺ and Fe³⁺, and the particles can be well suspended in cell culture medium. Photoluminescence analysis revealed that particles have prominent emissions at 536 nm, 590 nm, 615 nm, 650 nm and 695 nm upon excitation at a wavelength of 397 nm. Moreover, these Eu/Fe:HAp nanoparticles belonged to B-type carbonated HAp, which has been considered an effective biodegradable and biocompatible drug/gene carrier in biological applications.     

Deep Phenotyping of Superficial Epidermolytic Ichthyosis due to a Recurrent Mutation in KRT2

Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant inherited ichthyosis. SEI is caused by mutations in KRT2 and frequently shows erythroderma and widespread blistering at birth. We report the clinical manifestations of two patients from a Japanese family with SEI caused by a hotspot mutation, p.Glu487Lys, in KRT2. In addition, we summarize previous reports on SEI patients with the identical mutation. One of the two patients had disease onset at the age of 7 months. The other patient’s age of onset is unknown, but it was in childhood. Neither of the two patients showed erythroderma. To perform deep phenotyping, we studied the age of onset and the frequency of erythroderma in 34 reported SEI cases with the p.Glu487Lys mutation, including the present cases. Among the cases with sufficient clinical information, 44.4% of the cases that were due to p.Glu487Lys in KRT2 occurred at birth. Erythroderma was observed in 11.1% of the cases with p.Glu487Lys in KRT2.     

Development and field test of the articulated mobile robot T2 Snake-4 for plant disaster prevention

Abstract

In this work, we develop an articulated mobile robot that can move in narrow spaces, climb stairs, gather information, and operate valves for plant disaster prevention. The robot can adopt a tall position using a folding arm and gather information using sensors mounted on the arm. In addition, this paper presents a stair climbing method using a single backward wave. This method enables the robot to climb stairs that have a short tread. The developed robot system is tested in a field test at the World Robot Summit 2018, and the lessons learned in the field test are discussed.     

Small-angle X-ray scattering studies on melting and recrystallization behaviors of poly(oxyethylene) crystallites in poly(d,l-lactide)/poly(oxyethylene) blends

Direct determination of the discrete distribution for crystalline lamellar thickness has been performed for poly(d,l-lactic acid)/poly(oxyethylene) (PDLLA/PEG) blends by conducting small-angle X-ray scattering (SAXS) measurements using synchrotron radiation. The PDLLA used was an random (racemic) copolymer of bio-based poly(l-lactic acid) (PLLA) and poly(d-lactic acid) (PDLA) with the lactide monomer ratio of l:d = 50:50. It is known that PLA is miscible with PEG in the amorphous state. In the current paper, we report comprehensive results on structural analyses of PDLLA/PEG blends in the course of heating and cooling process using SAXS to elucidate the change in the thickness distribution of the lamellae. As a consequence, it was found that the distribution of the lamellar thickness moves toward the larger value (in other words, lamellar thickening) as temperature approaches the melting point. Typically, the thickness distribution was dispersed in the range of 10–20 nm at room temperature and it changed toward 40 nm in the vicinity of the melting temperature. To the best of our knowledge, this is the first report of direct determination of the discrete distribution for the crystalline lamellar thickness and their in-situ changes in the course of the lamellar thickening process. As a result, the lamellar thickening was found to occur at much lower temperature for the blend samples with 10% and 20% of PDLLA contents as compared to the PEG 100% sample. This phenomenon can be ascribed to the melting point depression owing to the miscibility between PEG and PDLLA. Thereby, thinner lamellae were melted and thicker ones appeared at much lower temperature for the blends than for the PEG 100% sample. As for the average repeating distance (long period) of the lamellar stacks, an abrupt increase similar to the critical divergence was observed (from 25 nm to 50 nm) in the heating process. Not only for the melting behavior but also in the course of recrystallization, change in the lamellar-thickness distribution was uncovered, which shows strong hysteresis depending on what temperature the sample was cooled down from.     

Poly(sulfonated phenylene)-block-poly(arylene ether sulfone) copolymer for polymer electrolyte fuel cell application

Novel poly(2-(3-sulfo)benzoyl-1,4-phenylene)-block-poly(arylene ether sulfone) copolymers (PSP-b-PAESs) were successfully synthesized by Ni(0)-catalyzed copolymerization of 2,5-dichloro-3′-sulfo-benzophenone (DCSB) and chlorobenzophenone-endcapped oligo(arylene ether sulfone). Their physical property, morphology and polymer electrolyte fuel cell (PEFC) performance were investigated compared to those of the DCSB-based random copolymers and Nafion112. PSP-b-PAES with a measured ion exchange capacity (IEC) of 1.82 meq g^?1, of which the hydrophilic/hydrophobic block lengths were evaluated as 17/8.4, showed the relatively small number of water molecules sorbed per sulfonic acid group (λ = 15) in water and the anisotropic membrane swelling with 2.4 times larger through-plane swelling than in-plane one, whereas it showed the almost isotropic proton conductivity. The PSP-b-PAES exhibited a microphase-separated structure composed of hydrophobic and hydrophilic domains, whereas the random copolymers exhibited a homogenous morphology. The PSP-b-PAES had the larger proton conductivity than the random copolymer with an IEC of 2.01 meq g^?1, especially under the low relative humidities. Even at a low humidification of 17% RH at 90 °C and 0.2 MPa, the PSP-b-PAES exhibited the high PEFC performance; namely, cell voltage of 0.69 V at load current density of 0.5 A cm^?2 and maximum output of 0.73 W cm^?2, which were much higher than those at 30% RH for the random copolymer (0.65 V and 0.51 W cm^?2) and Nafion112 (0.70 V and 0.61 W cm^?2). The PSP-b-PAES showed the fairly high durability of 750 h under PEFC operation at 90 °C in spite of the relatively low molecular weight. PSP-b-PAESs have the high potential as polymer electrolyte membrane for PEFC applications.