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.     

Molecular Features and Clinical Management of Hereditary Gynecological Cancers

Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li–Fraumeni, Cowden, and Peutz–Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests.     

Planar‐Chiral Cyclopentadienyl‐Ruthenium‐Catalyzed Regio‐ and Enantioselective Asymmetric Allylic Alkylation of Silyl Enolates under Unusually Mild Conditions

We report the asymmetric allylic alkylation of allylic chlorides with silyl enolates as a carbon nucleophile using a planar‐chiral cyclopentadienyl‐ruthenium (Cp′Ru) catalyst. The reaction proceeds under unusually mild conditions to give the desired branched products with complete regioselectivity and high enantioselectivity, and reactive functional groups, such as aldehyde, can be tolerated. In this reaction system, Cp′Ru plays an important role in activating both silyl enolate and allylic chloride.

     

Comparison Measurements for the Development of High-Temperature Platinum Resistance Scale

This paper describes measurements aimed to develop the high-temperature scale for high-temperature standard platinum resistance thermometers (HT-SPRTs). A furnace designed to facilitate comparison of a radiation thermometer with a HT-SPRT was developed for this work. The measurement uncertainty of the comparison is first reported, and then the comparison results for eight HT-SPRTs for temperatures from 660 °C up to 1040 °C are presented. Two different methods were adopted to analyze the comparison results. Upon discussion of the comparison results and adopting the second method to analyze the data, a correction term to the reference function of HT-SPRTs for temperatures above the current high-temperature limit, the Ag freezing point (961.78 °C), is suggested, as a preliminary result upon seeking the possibility to propose the extension of the platinum resistance thermometer scale. The two irregular cases for discussion of the criteria for interpolating HT-SPRTs of the current International Temperature Scale of 1990 (ITS-90) are also discussed.     

Propagation and structure of streamers in liquid dielectrics

Our purpose is to present a critical review of the current understanding of streamer propagation in dielectric liquids in order to help define the direction of future research. We show that the molecular structure has a significant effect on streamer propagation. The main parameter affecting propagation is the electronic affinity of the liquid molecules     

Kinetic diversity in the fusion of exocytotic vesicles

Age is the most important factor for the durability of biological valves. With an original design the Carpentier-Edwards pericardial valve showed improved results at 10 years. The influence of age on valve related complications is studied with a 10 year follow up on 807 valvular replacements. METHODS: Between January 1984 and December 1993, 807 patients underwent valve replacements with a Carpentier-Edwards pericardial bioprosthesis. Patients, 193 were younger than 60 years, 284 between 60 and 70 years and 330 patients were older than 70 years. All patients but seven were followed up for an average of 4.18 years after their operation and total follow up was 3373 patient years. Patients were divided into three groups of age: group I, less than 60 years; group II, 60-70 years; group III, over 70 years. A retrospective comparison was made between age groups. RESULTS: At 11 years, valve related complications included 97 patients with 27 valve related deaths. Rates of valve related death increase with age linearized rate were 0.3, 0.6 and 1.2%, respectively. No difference was observed for rates of all valve related morbidity: 2.6, 2.4 and 3.5%, respectively. Risk of thromboembolism increased with age, linearized rates were: 0.3, 0.7 and 1.3%. Risk of deterioration and reoperation decreased with age, rates of deterioration were 0.8, 0.1 and 0%. Other valve related events had the same incidence in all groups. No statistical difference was observed between group II and group III for deteriorations and reoperations. CONCLUSIONS: The performance of the Carpentier-Edwards pericardial valve is the same at 10 years in group II and III. This study supports the clinical use of this tissue valve in patients over 60 years. The results in group I are satisfactory, nevertheless, a more durable biological valve is needed for young patients.     

Rheological characterization of konjac glucomannan in concentrated solutions

Dynamic viscoelasticity measurements were performed for concentrated solutions of konjac glucomannan in an ionic liquid. The entanglement coupling appeared in the rheological data for each solution was characterized in terms of the molecular weight between entanglements (M _e) as an average size of the transient entanglement network. The value of M _e for konjac glucomannan in the molten state was estimated to be 1.8 × 10³ (in g mol^?1), being significantly smaller than that for cellulose, although the molecular weight and linkage of the repeating units were the same between these polysaccharides. This result suggested that the configuration of the repeating monosaccharide unit affected the entanglement network of these polysaccharides reflecting the single chain characteristics.     

The study of activity median aerodynamic diameter using imaging plate technique for assessment of effective dose from radon and its decay products

The indoor workplace environment was evaluated for exposure to radon and its decay products at two Universities in two metropolises of Japan. The mean radon concentrations in Nagoya University (NU) and Hokkaido University (HU) were 16.7 Bq m(-3) and 18.0 Bq m(-3), respectively. Activity median aerodynamic diameter (AMAD) of particles at NU ranged from 172 nm approximately 205 nm and at HU from 186 nm approximately 300 nm. Estimated effective doses for five usual sites of NU by ICRP approach was 0.15 mSvy(-1) approximately 0.76 mSvy(-1) and by UNSCEAR approach was 0.05 mSvy(-1) approximately 0.24 mSvy(-1). The effective dose for the same of HU by ICRP 66 approach was 0.16 mSvy(-1) approximately 0.79 mSvy(-1) and by UNSCEAR 2000 approach was 0.05 mSv y(-1) to 0.26 mSv y(-1). The two approaches differs on an average by a factor 2.3- approximately 4.7. The AMAD of obtained particle size distribution at NU has an average total deposition of 23% in human respiratory tract and 20% at HU.     

The weather dependence of particle size distribution of indoor radioactive aerosol associated with radon decay products

This study was performed to measure the activity size distribution of aerosol particles associated with short-lived radon decay products in indoor air at Nagoya University, Nagoya, Japan. The measurements were performed using a low pressure Andersen cascade impactor under variable meteorological conditions. The results showed that the greatest activity fraction was associated with aerosol particles in the accumulation size range (100-1000 nm) with a small fraction of nucleation mode (10-100 nm). Regarding the influence of the weather conditions, the decrease in the number of accumulation particles was observed clearly after rainfall without significant change in nucleation particles, which may be due to a washout process for the large particles.     

Resolution of Epoxydienes by Reversed-Phase Chiral HPLC and its Application to Stereochemistry Assignment of Mulberry Looper Sex Pheromone

Resolution of insect pheromonal cis-epoxydiene racemates derived from (Z,Z,Z)-3,6,9-trienes was examined with a reversed-phase chiral HPLC column. The results showed that a Chiralcel OJ-R column was suitable for separating the enantiomers having a C₁₇–C₂₃ unsaturated straight chain except for 9,10-epoxydienes with a C₂₁–C₂₃ chain. To determine the absolute configuration of the separated enantiomers, each of the optically active epoxydienes was hydrogenated over Pd-BaSO₄ and its behavior was examined on this chiral column by cochromatography with the corresponding chiral epoxy compound having a saturated chain, which was prepared via a Sharpless epoxidation reaction. This analysis showed that the dextrorotatory C₁₇–C₂₃ 3,4- and 6,7-epoxydienes and C₁₇–C₂₀ 9,10-epoxydienes with shorter R _ts possess (3S,4R)-, (6S,7R)-, and (9R,10S) configurations, respectively, and the levorotatory enantiomers with longer R _ts possess the opposite configuration. An abdominal tip extract of the mulberry looper, Hemerophila artilineata Butler (Lepidoptera: Geometridae: Ennominae), included (9S,10R)-(Z,Z)-cis-9,10-epoxy-3,6-octadecadiene as a main sex pheromone component. The synthetic (9S,10R)-9,10-epoxydiene, rather than its antipode, elicited strong antennal and behavioral responses from the male moths in electrophysiological and field tests.