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.     

Broadband bowtie belt nanoantennas

In this article, we study a linear array of bowtie nanoantennas placed between two metallic strips that can work from 800 to 1420 nm (600 nm linewidth), with an electric field enhancement factor close to 20. We study the dynamical change of the position of the electric field enhancement amongst different elements in the array and, at the same time, the effects of dispersion on the scalability of the array elements. A systematic analysis and methodology to produce an array that can operate over a large bandwidth whilst maintaining the electric field enhancement without significant variation is provided.     

Protection against adoptive transfer of autoimmune diabetes mediated through very late antigen-4 integrin

The very late antigen-4 (VLA-4) integrin expressed on the surface of lymphocytes and macrophages can regulate their migration to inflammatory sites as well as control cellular activation. The role of VLA-4 in the establishment of autoimmune diabetes is not easily predicted given the multiplicity of adhesion pathways and their differential use by various cell types. The contribution of VLA-4 to insulin-dependent diabetes mellitus was investigated by administration of VLA-4-specific monoclonal antibodies (MoAb) in an adoptive transfer model of disease in NOD mice. This study shows that VLA-4-specific MoAbs profoundly inhibit the development of diabetes with protection sustained by repeated MoAb exposure. Insulitis was completely inhibited during treatment and progressed to a severe degree once MoAb treatment was suspended, yet approximately 40% of treated recipients failed to become diabetic during 1-2 months post-treatment. Although we cannot rule out depletion of a relatively minor subpopulation of cells by prolonged anti-VLA-4 MoAb exposure, this inhibition of diabetes onset by treatment with MoAbs to VLA-4 supports a dependence on VLA-4 for cellular functions leading to diabetes and demonstrates that a significant disease modifying effect can be mediated by targeting the VLA-4 integrin.     

Preparation of pyrochlores. A1−xHxTaO3·nH2O (A=Na,K)

Pyrochlores of A_1?xH_xTaO₃·nH₂O (A=Na,K) were prepared under the hydrothermal conditions. The values of x for these compounds were increased from 0.3 to 0.5 for A=Na and from 0.2 to 0.5 for A=K by treatment with the distilled water. The compounds with x<0.5 were decomposed to a mixture of NaTaO₃ and Na₂Ta₄O₁₁ for A=Na, or to a mixture of KTaO₃ and a tetragonal tungsten bronze phase, and those with x=0.5 to a single phase of A₂Ta₄O₁₁ at elevated temperatures. Below the decomposition temperatures, defect pyrochlores with oxygen vacancies, $\text{A}{}_{\mathrm{<mtext>1?</mtext><mtext>x</mtext>}}\text{TaO}{}_{\mathrm{<mtext>3?</mtext><mtext>x</mtext><mtext>2</mtext>}}$, were produced. They were hygroscopic, and in the case of A=K and x=0.5 the original phase was recovered by leaving in air for several hours.     

Cooperative behavior of various agents in dynamic environment

The multi-agent model is a model in which agents with limited ability cooperate each other to accomplish a goal. In this paper, we introduce a multi-agent model in which agents are created to imitate real ants. There are two different type of agents, each type of which has a particular task. We designed agents to communicate each other by using pheromone considering noise. On this model, we observed cooperative behavior of agents and evaluated conditions to make an order of behavior in the model.     

The effect of furosemide on evoked otoacoustic emissions in guinea pigs

After recording transiently evoked otoacoustic emissions (TEOAEs) to a click stimulus in guinea pigs by using the IL088 which was developed by Bray and Kemp (1987) for easy recording and analysis of TEOAE, the changes after intravenous administration of furosemide (30 mg/kg or 50 mg/kg) were examined. The wave of the TEOAE could be detected from 20 of 24 ears (83%). After the i.v. injection of furosemide (30 mg/kg), TEOAE powers (total echo power and highest peak power in FFT pictures) decreased quickly and showed minimum values after 5-10 min. Then they increased rapidly and recovered normally within 60 min after injection. However, no ears showed TEOAEs during the 5- to 10-min period following the injection of the 50-mg/kg dose of furosemide. They then recovered slowly as compared with the group treated with the lower dose of furosemide (30 mg/kg). These changes are similar to those of the endocochlear potential (EP) after furosemide injection. These data support the notion that the EP can contribute to the mechanism of TEOAE generation.