DEVELOPMENT OF A TABLE TENNIS MACHINE TO COUNTER THE “CHIQUITA” SPIN

After Beijing Olympics, leading athletes began to use a stroke known as the “Chiquita” spin frequently. Thus, the Japan national table tennis team at the time undertook countermeasures against the Chiquita spin including some plans. However, these did not produce significant results. Therefore, we developed a table tennis training machine for the team in activities supporting the Japan national table tennis team. The machine has 3 rotors to shoot a ball stably. Also, these rotors are twisted to make a “gyro rotation” of the ball. This machine was introduced into the Japan national table tennis team to take measures for London 2012 Olympic

Receptor Autoradiographic Analysis of Muscarinic Receptors in the Rat Atrioventricular Node

We carried out investigations on muscarinic acetylcholine receptors (m-AChR) in the rat heart, including the atrioventricular (AV) node. The related tissue sections were incubated with 3H-quinuclidinyl benzilate (3H-QNB), then autoradiography and an image analysis coupled with computer-assisted microdensitometry were done. A single type of specific and high affinity binding sites of 3H-QNB was found to be highly concentrated in the AV node, the maximum binding capacity (Bmax) being 1.4 pmol/mg protein and with a dissociation constant (Kd) of 0.5 nM. The density and affinity of the binding to the AV node were the highest, when compared with findings in the atrium (interatrial septum) and ventricle (interventricular septum). The binding was competitively displaced by AF-DX 116, a selective antagonist for the M2 AChR subtype, with a high affinity, whereas pirenzepine, an antagonist for the M1 AChR subtype was much less potent in displacing the binding. Therefore, vagal-cholinergic stimulation presumably plays a significant role in functions of the rat AV node, probably by interacting with the specific, high affinity M2 AChR subtype

Development of an experimental platform for combinative use of an XFEL and a high-power nanosecond laser

We developed an experimental platform for combinative use of an X-ray free electron laser (XFEL) and a high-power nanosecond laser. The main target of the platform is an investigation of matter under high-pressure states produced by a laser-shock compression. In this paper, we show details of the experimental platform, including XFEL parameters and the focusing optics, the laser irradiation system and X-ray diagnostics. As a demonstration of the high-power laser-pump XFEL-probe experiment, we performed an X-ray diffraction measurement. An in-situ single-shot X-ray diffraction pattern expands to a large angle side, which shows a corundum was compressed by laser irradiation.Inubushi, Y.; Yabuuchi, T.; Togashi, T.; Sueda, K.; Miyanishi, K.; Tange, Y.; Ozaki, N.; Matsuoka, T.; Kodama, R.; Osaka, T.; Matsuyama, S.; Yamauchi, K.; Yumoto, H.; Koyama, T.; Ohashi, H.; Tono, K.; Yabashi, M. Development of an Experimental Platform for Combinative Use of an XFEL and a High-Power Nanosecond Laser. Appl. Sci. 2020, 10, 2224. https://doi.org/10.3390/app10072224

Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders

Intracellular trafficking of receptor proteins is essential for neurons to detect various extracellular factors during the formation and refinement of neural circuits. However, the precise mechanisms underlying the trafficking of neurotrophin receptors to synapses remain elusive. Here, we demonstrate that a brain-enriched sorting nexin, ARHGAP33, is a new type of regulator for the intracellular trafficking of TrkB, a high-affinity receptor for brain-derived neurotrophic factor. ARHGAP33 knockout (KO) mice exhibit reduced expression of synaptic TrkB, impaired spine development and neuropsychiatric disorder-related behavioural abnormalities. These deficits are rescued by specific pharmacological enhancement of TrkB signalling in ARHGAP33 KO mice. Mechanistically, ARHGAP33 interacts with SORT1 to cooperatively regulate TrkB trafficking. Human ARHGAP33 is associated with brain phenotypes and reduced SORT1 expression is found in patients with schizophrenia. We propose that ARHGAP33/SORT1-mediated TrkB trafficking is essential for synapse development and that the dysfunction of this mechanism may be a new molecular pathology of neuropsychiatric disorders

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Transition of the Interface between Iron and Carbide Precipitate From Coherent to Semi-Coherent

There are some precipitates that undergo transition from a coherent to semi-coherent state during growth. An example of such a precipitate in steel is carbide with a NaCl-type structure, such as TiC and NbC. The interface energy between carbide precipitate and iron is obtained via large-scale first-principles electronic structure calculation. The strain energy is estimated by structure optimization of the iron matrix with virtual carbide precipitate using the empirical potential. The transition of the interface from a coherent to semi-coherent state was examined by comparing the interface and strain energies between the coherent and semi-coherent interfaces. The sizes where both the precipitates undergo this transition are smaller than those of the interfaces with minimum misfit. The estimated transition diameter of TiC is in agreement with the experimentally obtained value