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.     

Analysis of indoor PM2.5 exposure in Asian countries using time use survey

Most household fuels used in Asian countries are solid fuels such as coal and biomass (firewood, crop residue and animal dung). The particulate matter (PM), CO, NOx and SOx produced through the combustion of these fuels inside the residence for cooking and heating has an adverse impact on people's health. PM 2.5 in particular, consisting of particles with an aerodynamic diameter of 2.5 μm or less, penetrates deep into the lungs and causes respiratory system and circulatory system diseases and so on. As a result, the World Health Organization (WHO) established guideline values for this type of particulate matter in 2005. In this study, the authors focused on PM 2.5 and estimated indoor exposure concentrations for PM 2.5 in 15 Asian countries. For each environment used for cooking, eating, heating and illumination in which people are present temporarily (microenvironment), exposure concentrations were estimated for individual cohorts categorized according to sex, age and occupation status. To establish the residence time in each microenvironment for each of the cohorts, data from time use surveys conducted in individual countries were used. China had the highest estimate for average exposure concentration in microenvironment used for cooking at 427.5 μg/m³ , followed by Nepal, Laos and India at 285.2 μg/m³, 266.3 μg/m³ and 205.7 μg/m³ , respectively. The study found that, in each country, the PM2.5 exposure concentration was highest for children and unemployed women between the ages of 35 and 64. The study also found that the exposure concentration for individual cohorts in each country was greatly affected by people's use of time indoors. Because differences in individual daily life activities were reflected in the use of time and linked to an assessment of exposure to indoor air-polluting substances, the study enabled detailed assessment of the impact of exposure.     

Determination of γ-glutamyl-valyl-glycine in raw scallop and processed scallop products using high pressure liquid chromatography–tandem mass spectrometry

The determination of the kokumi peptide, γ-glutamyl-valyl-glycine (γ-Glu-Val-Gly) in raw scallop and processed scallop products was carried out using high pressure liquid chromatography–tandem mass spectrometry (LC/MS/MS). The detection of γ-Glu-Val-Gly was achieved using a multiple reaction monitoring (MRM) method. The optimised condition enabled the precise determination of γ-Glu-Val-Gly. Raw scallop contained 0.08 μg/g γ-Glu-Val-Gly, and the γ-Glu-Val-Gly levels in processed scallop products, such as dried-scallop and scallop extract, were measured to be 0.64 and 0.77 μg/g, respectively. This is the first report to confirm the existence of γ-Glu-Val-Gly in foodstuff.     

Hetero-stereocomplex formation of stereoblock copolymer of substituted and non-substituted poly(lactide)s

The crystallization behavior of the stereoblock copolymer of substituted and non-substituted poly(lactide)s, i.e., poly(d-2-hydroxybutyrate) and poly(l-lactide) chains having the opposite configurations [P(D-2HB)-b-PLLA] and the reference block copolymer of poly(d-2-hydroxybutyrate) and poly(d-lactide) chains with the identical configurations [P(D-2HB)-b-PDLA] was investigated. At the crystallizable temperature range of 60-160 °C, the crystallized P(D-2HB)-b-PLLA contained solely the hetero-stereocomplex crystallites as a crystalline species, without formation of poly(d-2-hydroxybutyrate) or poly(l-lactide) homo-crystallites, in contrast with their polymer blends. On the other hand, at the crystallizable temperature range of 60-140 °C, the crystallized P(D-2HB)-b-PDLA had only PDLA homo-crystallites as crystalline species, reflecting no co-crystallites formation between poly(d-2-hydroxybutyrate) and poly(d-lactide) chains having the same configurations. The equilibrium melting temperature of hetero-stereocomplex crystallites in P(D-2HB)-b-PLLA was 189.0 °C, which was higher than 171.3 °C of PDLA homo-crystallites in P(D-2HB)-b-PDLA. Although the final crystallinity of P(D-2HB)-b-PLLA was higher than those of P(D-2HB)-b-PDLA, the spherulite growth rate of P(D-2HB)-b-PLLA was lower.The regime analysis indicated unusual nucleation mechanism of P(D-2HB)-b-PLLA.     

Proposal of Design Criteria for Gas Entrainment from Vortex Dimples Based on a Computational Fluid Dynamics Method

Design criteria for gas entrainments (GE) from the liquid surface in a fast breeder reactor system were proposed in this paper for the two types of GE phenomena from a vortex dimple based on a computational fluid dynamics (CFD) method. The first gas entrainment phenomenon is a gas core extension directly to the outlet piping level, which induces large amount of GE to the flow system. The second is continuous bubble detachments from the tip of the vortex dimple. Based on CFD calculations for elemental experiments of the surface vortex, local CFD non-dimensional numbers were defined as the design criteria to prevent GE. In conclusion, it was found that the CFD non-dimensional numbers are useful for the design parameters of GE prevention.     

Dendrite growth processes of silicon and germanium from highly undercooled melts

The crystal growth behavior of a semiconductor from a very highly undercooled melt is expected to be different from that of a metal. In the present experiment, highly pure undoped Si and Ge were undercooled by an electromagnetic levitation method, and their crystal growth velocities (V) were measured as a function of undercooling (ΔT). The value of V increased with ΔT, and V=26 m/s was observed at ΔT=260 K for Si. This result corresponds well with the predicted value based on the dendrite growth theory. The growth behaviors of Si and Ge were found to be thermally controlled in the measured range of undercooling. The microstructures of samples solidified from undercooled liquid were investigated, and the amount of dendrites immediately after recalescence increased with undercooling. The dendrite growth was also observed by a high-speed camera.     

A low-carbon scenario creation method for a local-scale economy and its application in Kyoto city

On May 2008, Kyoto city government set up a low-carbon target of a 50% GHG reduction by 2030 compared to the 1990 level. To contribute to these discussions, we developed a local (city-scale) low-carbon scenario creation method. An estimation model was developed to show a quantitative and consistent future snapshot. The model can explicitly treat the uncertainty of future socio-economic situations, which originate from the openness of local economy. The method was applied to Kyoto city, and countermeasures to achieve the low-carbon target were identified. Without countermeasures, emissions would increase 12% from 2000. Among the measures, the reduction potential of energy efficiency improvements to residential and commercial sectors was found to be relatively large (15% and 18% of total reductions, respectively). The reduction potential of the passenger transport sector, in which the city government's policy is especially important, was 17% of the total amount. A sensitivity analysis showed that a 10% increase in exports leads to an 8.5% increase in CO₂ emissions, and a 20% increase in the share of the commuters from outside the city leads to a 3.5% decrease of CO₂ emissions because of the smaller number of residents in the city.