Hybrid ubiquinone: novel inhibitor of mitochondrial complex I

AbstractWe synthesized novel ubiquinone analogs by hybridizing the natural ubiquinone ring (2,3-dimethoxy-5-methyl-1,4-benzoquinone) and hydrophobic phenoxybenzamide unit, and named them hybrid ubiquinones (HUs). The HUs worked as electron transfer substrates with bovine heart mitochondrial succinate–ubiquinone oxidoreductase (complex II) and ubiquinol–cytochrome c oxidoreductase (complex III), but not with NADH–ubiquinone oxidoreductase (complex I). With complex I, they acted as inhibitors in a noncompetitive manner against exogenous short-chain ubiquinones irrespective of the presence of the natural ubiquinone ring. Elongation of the distance between the ubiquinone ring and the phenoxybenzamide unit did not recover the electron accepting activity. The structure/activity study showed that high structural specificity of the phenoxybenzamide moiety is required to act as a potent inhibitor of complex I. These findings indicate that binding of the HUs to complex I is mainly decided by some specific interaction of the phenoxybenzamide moiety with the enzyme. It is of interest that an analogous bulky and hydrophobic substructure can be commonly found in recently registered synthetic pesticides the action site of which is mitochondrial complex I

COVID-19 and heat illness in Tokyo, Japan: implications for the summer Olympic and Paralympic Games in 2021

The 2020 summer Olympic and Paralympic Games in Tokyo were postponed to July– September 2021 due to the coronavirus disease 2019 (COVID-19) pandemic. While COVID-19 has emerged as a monumental health threat for mass gathering events, heat illness must be acknowl-edged as a potentially large health threat for maintaining health services. We examined the number of COVID-19 admissions and the Tokyo rule for emergency medical care, in Tokyo, from March to September 2020, and investigated the weekly number of emergency transportations due to heat illness and weekly averages of the daily maximum Wet Bulb Globe Temperature (WBGT) in Tokyo in the summer (2016–2020). The peak of emergency transportations due to heat illness overlapped the resurgence of COVID-19 in 2020, and an increase of heat illness patients and WBGT has been observed. Respect for robust science is critical for the decision-making process of mass gathering events during the pandemic, and science-based countermeasures and implementations for COVID-19 will be warranted. Without urgent reconsiderations and sufficient countermeasures, the double burden of COVID-19 and heat-related illnesses in Tokyo will overwhelm the healthcare provision system, and maintaining essential health services will be challenging during the 2021 summer Olympic and Paralympic Games

Twenty barrel in situ pipe gun type solid hydrogen pellet injector for the Large Helical Device

A 20 barrel solid hydrogen pellet injector, which is able to inject 20 cylindrical pellets with a diameter and length of between 3.0 and 3.8 mm at the velocity of 1200 m/s, has been developed for the purpose of direct core fueling in LHD (Large Helical Device). The in situ pipe gun concept with the use of compact cryo-coolers enables stable operation as a fundamental facility in plasma experiments. The combination of the two types of pellet injection timing control modes, i.e., pre-programing mode and real-time control mode, allows the build-up and sustainment of high density plasma around the density limit. The pellet injector has demonstrated stable operation characteristics during the past three years of LHD experiments

サイガイジ ノ ショクジ ニカンスル ケントウ : ヤサイ クダモノ セシュ オヨビ ビタミンC ノ カクホ ニオケル シンクウ チョウリ ノ ユウコウセイ トコンダテ エノ オウヨウ

As one method of preventing unbalanced diet and vitamin deficiency caused by not eating enough fruits and vegetables in temporary shelters at the time of disaster, the effectiveness of vacuum cooking method was studied. Since preparing food on site under sanitary environment is difficult with limited water and food resources, food preparation procedure in emergency was also re-examined and effectiveness of adding food cooked by vacuum cooking method was discussed.It was observed that, in food cooked under vacuum cooking method, no bacteria propagated for 15 days and the loss of vitamin C was controlled. This suggested that food cooked under vacuum cooking method could be preserved for a longer period of time and thus transported to the disaster site where lifeline is destroyed. In addition, almost all panels who participated in the sensory test preferred the vacuum-packed cabbages and apples due to maintaining their original texture.The result suggested that, in the disaster-stricken area where lifeline is destroyed, the use of vacuum cooking method was effective in preventing unbalanced diet and lack of intaking vegetables, fruits and vitamin C

Single-cell dynamics of pannexin-1-facilitated programmed ATP loss during apoptosis

死にゆく細胞のATP濃度変化を詳細に可視化することに成功 --積極的にATP濃度を下げる因子を明らかに--. 京都大学プレスリリース. 2020-10-22.ATP is essential for all living cells. However, how dead cells lose ATP has not been well investigated. In this study, we developed new FRET biosensors for dual imaging of intracellular ATP level and caspase-3 activity in single apoptotic cultured human cells. We show that the cytosolic ATP level starts to decrease immediately after the activation of caspase-3, and this process is completed typically within 2 hr. The ATP decrease was facilitated by caspase-dependent cleavage of the plasma membrane channel pannexin-1, indicating that the intracellular decrease of the apoptotic cell is a ‘programmed’ process. Apoptotic cells deficient of pannexin-1 sustained the ability to produce ATP through glycolysis and to consume ATP, and did not stop wasting glucose much longer period than normal apoptotic cells. Thus, the pannexin-1 plays a role in arresting the metabolic activity of dead apoptotic cells, most likely through facilitating the loss of intracellular ATP

Gender with marital status, cultural differences, and vulnerability to hypertension: Findings from the national survey for noncommunicable disease risk factors and mental health using WHO STEPS in Bhutan

Cardiovascular disease is the leading cause of death in the Kingdom of Bhutan. Thus, the early detection and prevention of hypertension is critical for reducing cardiovascular disease. However, the influence of sociocultural factors on vulnerability to hypertension needs further investigation. This study performed secondary data analysis on 1, 909 individuals in a cross-sectional study (the National survey for noncommunicable disease risk factors and mental health using World Health Organization (WHO) STEPS approach in Bhutan– 2014). Multivariate logistic regression demonstrated a significant association between gender with marital status and hypertension. Women had a higher odds ratio than men (Ref) when married (AOR: 1.27, 95% confidence intervals (CI): 1.23–1.31), and when separated, divorced, or widowed (AOR: 1.18, 95% CI: 1.12–1.26). People who speak the Tshanglakha language scored the highest odds (AOR: 1.24, 95% CI: 1.20–1.27), followed by Lhotshamkha (AOR: 1.09, 95% CI: 1.06–1.12) and Dzongkha (Ref) after adjusting for various social and biomedical factors. Additionally, tobacco use displayed decreased odds for hypertension. To promote the early detection and prevention of hypertension, these cultural factors should be considered even within small geographic areas, such as Bhutan. It is necessary to strengthen hypertension preventive strategies for people who speak Tshanglakha and Lhotshamkha. Furthermore, careful consideration should be given to preventing hypertension among adults aged 40 years or more, women who are married, separated, divorced, or widowed, and men who never married in Bhutan

NB-LRR-encoding genes conferring susceptibility to organophosphate pesticides in sorghum

Organophosphate is the commonly used pesticide to control pest outbreak, such as those by aphids in many crops. Despite its wide use, however, necrotic lesion and/or cell death following the application of organophosphate pesticides has been reported to occur in several species. To understand this phenomenon, called organophosphate pesticide sensitivity (OPS) in sorghum, we conducted QTL analysis in a recombinant inbred line derived from the Japanese cultivar NOG, which exhibits OPS. Mapping OPS in this population identified a prominent QTL on chromosome 5, which corresponded to Organophosphate-Sensitive Reaction (OSR) reported previously in other mapping populations. The OSR locus included a cluster of three genes potentially encoding nucleotide-binding leucine-rich repeat (NB-LRR, NLR) proteins, among which NLR-C was considered to be responsible for OPS in a dominant fashion. NLR-C was functional in NOG, whereas the other resistant parent, BTx623, had a null mutation caused by the deletion of promoter sequences. Our finding of OSR as a dominant trait is important not only in understanding the diversified role of NB-LRR proteins in cereals but also in securing sorghum breeding free from OPS