Screening for cold tolerance genes in C. elegans, whose expressions are affected by anticancer drugs camptothecin and leptomycin B

Okahata M., Sawada N., Nakao K., et al. Screening for cold tolerance genes in C. elegans, whose expressions are affected by anticancer drugs camptothecin and leptomycin B. Scientific Reports 14, 5401 (2024); https://doi.org/10.1038/s41598-024-55794-z.Temperature is a vital environmental factor affecting organisms’ survival as they determine the mechanisms to tolerate rapid temperature changes. We demonstrate an experimental system for screening chemicals that affect cold tolerance in Caenorhabditis elegans. The anticancer drugs leptomycin B and camptothecin were among the 4000 chemicals that were screened as those affecting cold tolerance. Genes whose expression was affected by leptomycin B or camptothecin under cold stimuli were investigated by transcriptome analysis. Abnormal cold tolerance was detected in several mutants possessing genes that were rendered defective and whose expression altered after exposure to either leptomycin B or camptothecin. The genetic epistasis analysis revealed that leptomycin B or camptothecin may increase cold tolerance by affecting a pathway upstream of the insulin receptor DAF-2 that regulates cold tolerance in the intestine. Our experimental system combining drug and cold tolerance could be used for a comprehensive screening of genes that control cold tolerance at a low cost and in a short time period

Synaptic Polarity Depends on Phosphatidylinositol Signaling Regulated by myo-Inositol Monophosphatase in Caenorhabditis elegans

Although neurons are highly polarized, how neuronal polarity is generated remains poorly understood. An evolutionarily conserved inositol-producing enzyme myo-inositol monophosphatase (IMPase) is essential for polarized localization of synaptic molecules in Caenorhabditis elegans and can be inhibited by lithium, a drug for bipolar disorder. The synaptic defect of IMPase mutants causes defects in sensory behaviors including thermotaxis. Here we show that the abnormalities of IMPase mutants can be suppressed by mutations in two enzymes, phospholipase Cβ or synaptojanin, which presumably reduce the level of membrane phosphatidylinositol 4,5-bisphosphate (PIP2). We also found that mutations in phospholipase Cβ conferred resistance to lithium treatment. Our results suggest that reduction of PIP2 on plasma membrane is a major cause of abnormal synaptic polarity in IMPase mutants and provide the first in vivo evidence that lithium impairs neuronal PIP2 synthesis through inhibition of IMPase. We propose that the PIP2 signaling regulated by IMPase plays a novel and fundamental role in the synaptic polarity

The Transition of the Motor Ability of Schoolchildren from the Forest Kindergarten

本研究では森の幼稚園を卒園した小学生（１～５年生）を対象に，小学校で行われる新体力テスト（８種目）の結果を質問紙で問い，その結果をまとめることで，森の幼稚園を卒園した小学生の体力・運動能力の推移を明らかにした。2010年度から2014年度までの卒園児162名を対象に，５年間分，通算293名分（同一児童のデータが異なる学年でカウントされている）のデータを収集した。その結果，入学後１年から数年の時点では森の幼稚園の卒園児は体力・運動能力が全国平均よりも高いが，学年が上がるにつれて平均的な成績になるという傾向が現れた。これは，久原ほか（2015）で提起された，森の幼稚園の卒園児の体力・運動能力は小学校入学後すぐには平均的であるが，数年を経てから平均よりも高くなるという仮説とは相反する結果であった。本研究では，特に1,2年生時点の平均値において，前出の久原ほか（2015）の３倍以上の標本数となっており，より信頼性の高いものであると考えられる。今後は，中・高学年においても標本数を増加させて，より信頼性の高いデータから，森の幼稚園の卒園児の体力・運動能力の推移を明らかにする必要がある。This study aimed to reveal the transition of the motor ability of schoolchildren from Forest Kindergarten, Japan. In total, 162 children who had graduated from Forest Kindergarten were asked to answer a questionnaire about their motor ability. The results indicated that first - to second - year students had higher levels of motor ability than the national average. Third - to fifth - year students had ordinary levels of motor ability. A tendency for the level of motor ability to decline was revealed. This conclusion contradicts the hypothesis that Kuhara et al. (2015) have proposed. However the present study can be considered more reliability than that of Kuhara et al. (2015), because it had more than three times the sample size

Novel and Conserved Protein Macoilin Is Required for Diverse Neuronal Functions in Caenorhabditis elegans

Neural signals are processed in nervous systems of animals responding to variable environmental stimuli. This study shows that a novel and highly conserved protein, macoilin (MACO-1), plays an essential role in diverse neural functions in Caenorhabditis elegans. maco-1 mutants showed abnormal behaviors, including defective locomotion, thermotaxis, and chemotaxis. Expression of human macoilin in the C. elegans nervous system weakly rescued the abnormal thermotactic phenotype of the maco-1 mutants, suggesting that macoilin is functionally conserved across species. Abnormal thermotaxis may have been caused by impaired locomotion of maco-1 mutants. However, calcium imaging of AFD thermosensory neurons and AIY postsynaptic interneurons of maco-1 mutants suggest that macoilin is required for appropriate responses of AFD and AIY neurons to thermal stimuli. Studies on localization of MACO-1 showed that C. elegans and human macoilins are localized mainly to the rough endoplasmic reticulum. Our results suggest that macoilin is required for various neural events, such as the regulation of neuronal activity

Bidirectional regulation of thermotaxis by glutamate transmissions in Caenorhabditis elegans

This paper provides a molecular and genetic analysis of the neural circuitry that regulates the migration of Caenorhabditis elegans towards either warmer or colder temperature and reveals an important role of glutamate signalling in this process

Development of a Multifunctional Lightweight Membrane with a High Specific Power Generation Capacity

As a lighter power generation system, Japan Aerospace Exploration Agency (JAXA) and Sakase Adtech Corp. are developing a demonstrator component named “Harvesting Energy with Lightweight Integrated Origami Structure” (HELIOS), which is a deployable lightweight membrane structure. HELIOS has solar arrays on its surface and demonstrates the technology which enables higher specific power generation capacity compared to the conventional solar array panels. The membrane also has communication antennas, showing the potency of lightweight membrane’s multifunctionality such as large data transmitting by 5G antennas and high-resolution observation by interferometer antennas. This paper presents the component’s concept and design, and the expected achievements