IL-21 is required for the maintenance and pathogenesis of murine Vγ4+ IL-17-producing γδT cells

Murine IL-17-producing γδT (γδT17) cells are divided into two subsets: natural γδT17 (nγδT17) cells, whose development is restricted to the fetal thymus, and inducible γδT17 cells, which require antigen exposure for their IL-17 production and are presumed to develop from Rorc+Il17a-CCR9+ immature γδT17 cells in the adult thymus and whose T cell receptor (TCR) is biased toward Vγ4. Although IL-23 is known to be involved in developing γδT17 cells, the roles of other cytokines, such as IL-21, which is involved in developing Th17 cells like IL-23, in the development, maintenance, and pathophysiology of γδT17 cells remain unknown. Here, we show that IL-21 is dispensable for the fetal thymic development of nγδT17 cells but is required for the peripheral maintenance of Vγ4+nγδT17 cells. Upon stimulation with γδTCR, IL-1 plus IL-21 induces the proliferation of Vγ4+nγδT17 cells via STAT3 as effectively as IL-1 plus IL-23. Using bone marrow chimeric mice, we demonstrated that immature γδT17 cells are produced de novo in the adult mice from donor adult bone marrow cells and that IL-21 is dispensable for their development. Instead, IL-21 is required to expand newly induced Vγ4+γδT17 cells in the periphery upon immunization. Finally, using adoptive transfer experiments of γδT17 cells, we found that IL-21 receptors on γδT17 cells are involved in maintaining Vγ4+γδT17 cells, subsequent infiltration of Th17 cells into the spinal cord, and exacerbation of experimental autoimmune encephalomyelitis. Collectively, IL-21 plays a vital role in the maintenance and pathogenesis of Vγ4+γδT17 cells

Methylation deficiency disrupts biological rhythms from bacteria to humans

メチル化と体内時計が生命誕生以来の密な関係にあることを発見 --生命の起源に学ぶヒト障害の新治療法--. 京都大学プレスリリース. 2020-05-27.The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies

Publisher Correction: Methylation deficiency disrupts biological rhythms from bacteria to humans

From Springer Nature via Jisc Publications RouterHistory: registration 2020-05-27, pub-electronic 2020-06-04, online 2020-06-04, collection 2020-12Publication status: PublishedAn amendment to this paper has been published and can be accessed via a link at the top of the paper

Nondestructive Detection of Cold Flakes in Aluminum Alloy Die-Cast Plate with Ultrasonic Measurement

Aluminum alloy die-cast plates (ADC 12) were subjected to ultrasonic measurement to obtain a relation between the intensity distribution of the ultrasonic wave and positions of cold flakes appearing in the plate for developing a nondestructive method to detect cold flakes in the diecasts. Die-cast plates of 170 mm in length, 50 mm in width and 6.8 mm in thickness were produced with wider gates to introduce larger cold flakes in the plate. Then the ultrasonic measurement was carried out with the immersion method by using a probe generating a longitudinal wave of 20 MHz in frequency. Intensity distributions of the ultrasonic wave were obtained from the surface to the bottom. The cross section analysis was carried out to examine the distribution of the cold flake. From the cross section analysis, three types of cold flakes were observed: the type A with a straight boundary of initial solidification with oxide thin layer, the type B with a straight boundary without oxide layer, and the type C of an irregular and wavy boundary without oxide layer. In the case of the type C, the oxide layer was thought to be out of the observed section. The ultrasonic wave was slightly reflected from the front and rear boundaries between the cold flake and the matrix, and it was found that the position and the thickness of the cold flake can be detected by ultrasonic measurement

Numerical Simulation of Toughening by Crack Deflection and Bowing of Glass Matrix-Alumina Particulate Composite

rights: 社団法人日本セラミックス協会 rights: 本文データは学協会の許諾に基づきCiNiiから複製したものである relation: isVersionOf: http://ci.nii.ac.jp/naid/110002291289/A numerical simulation of crack bowing and deflection was performed on glass matrix alumrnina particulate composite to evaluate the effects on these toughening mechanisms of composite and was compared with the experimental data of previous works by the authors. The numerical simulation revealed that a crack deflection was predominant in the fracture process of glass matrix alumina particulate composite and that the crack bowing hardly emerged. If it is assumed that the crack extended into all alumina particle, the crack bowing emerges. With an increase in the difference of the fracture toughness between the particles and the matrix, the toughening by crack bowing becomes more effective and is more effective than that by crack deflection. Under the assumption that the interfacial precipitation promotes the crack bowing, the results of the numerical simulation were in agreement with experimental data of the present authors