Variety of disk wind-driven explosions in massive rotating stars

We perform a set of two-dimensional, non-relativistic, hydrodynamics simulations for supernova-like explosion associated with stellar core collapse of rotating massive stars to a system of a black hole and a disk connected by the transfer of matter and angular momentum. Our model of the central engine also includes the contribution of the disk wind. In this work, we specifically investigate the wind-driven explosion of rotating, large-mass progenitor stars with the zero-age main-sequence mass of $M_\mathrm{ZAMS}=20\,M_\odot$ from arXiv:2008.09132 . This study is carried out using the open-source hydrodynamic code Athena++, for which we implement a method to calculate self-gravity for axially symmetric density distributions. We, then, investigate the explosion properties and the $^{56}$Ni production as a function of (varying) some features of the wind injection. We find a large variety of explosion energy with $E_\mathrm{expl}$ ranging from $\sim 0.049\times10^{51}$~erg to $\sim 34\times10^{51}$~erg and ejecta mass $M_\mathrm{ej}$ from 0.58 to 6 $M_\odot$, which shows a bimodal distribution in high- and low-energy branches. We demonstrate that the resulting outcome of a highly- or sub-energetic explosion for a certain stellar structure is mainly determined by the competition between the ram pressure of the injected matter and that of the infalling envelope. In the nucleosynthesis analysis the $^{56}$Ni mass produced in our models goes from $< 0.2~M_\odot$ in the sub-energetic explosions to $2.1~M_\odot$ in the highly-energetic ones. These results are consistent with the observational data of stripped-envelope and high-energy SNe such as broad-lined type Ic SNe. However, we find a tighter correlation between the explosion energy and the ejecta mass than that observationally measured.Comment: published by MNRAS, 18 pages, 15 figures, 2 tables, comments welcom

The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal

In behavioral learning, reward-related events are encoded into phasic dopamine (DA) signals in the brain. In particular, unexpected reward omission leads to a phasic decrease in DA (DA dip) in the striatum, which triggers long-term potentiation (LTP) in DA D2 receptor (D2R)-expressing spiny-projection neurons (D2 SPNs). While this LTP is required for reward discrimination, it is unclear how such a short DA-dip signal (0.5–2 s) is transferred through intracellular signaling to the coincidence detector, adenylate cyclase (AC). In the present study, we built a computational model of D2 signaling to determine conditions for the DA-dip detection. The DA dip can be detected only if the basal DA signal sufficiently inhibits AC, and the DA-dip signal sufficiently disinhibits AC. We found that those two requirements were simultaneously satisfied only if two key molecules, D2R and regulators of G protein signaling (RGS) were balanced within a certain range; this balance has indeed been observed in experimental studies. We also found that high level of RGS was required for the detection of a 0.5-s short DA dip, and the analytical solutions for these requirements confirmed their universality. The imbalance between D2R and RGS is associated with schizophrenia and DYT1 dystonia, both of which are accompanied by abnormal striatal LTP. Our simulations suggest that D2 SPNs in patients with schizophrenia and DYT1 dystonia cannot detect short DA dips. We finally discussed that such psychiatric and movement disorders can be understood in terms of the imbalance between D2R and RGS

酢酸の有する呈味発現機構の解析

学位の種別:論文博士University of Tokyo(東京大学

Otolith strontium : calcium ratios in a freshwater stingray, Himantura signifer Compagno and Roberts, 1982, from the Chao Phraya River, Thailand

Otolith microchemistry was examined in a freshwater stingray, Himantura signifer, collected from a freshwater region of the Chao Phraya River, Thailand. Otoliths of H. gerarudii and H. imbricata from the estuary at the mouth of the Chao Phraya River, and H. imbricata from the sea adjacent to the river mouth were also examined. Otolith Ca concentration was almost constant among the three species, regardless of their habitat environments. In contrast, Sr concentration and the Sr : Ca ratio differed considerably among the species, those of the freshwater species being at the lowest levels and that of the marine population of H. imbricata the highest. Intraspecific variation in Sr concentrations and Sr : Ca ratios found in H. imbricata from estuarine and marine environments suggested that those levels varied according to the habitat. Otolith Sr concentrations and Sr : Ca ratios of male freshwater stingrays increased with body growth, whereas those of female otoliths decreased temporarily to the lowest level in 250-300 mm disk width (mature) specimens. The findings suggested that H. signifer from freshwater regions enter a brackish or seawater environment at some time in their life history. The marked fluctuations in Sr concentration and Sr : Ca ratio in female otoliths may be related to presumed reproductive behavior, such as ceasing migration across a saline boundary during the reproductive period and giving birth in a freshwater region of the river, or may have been affected by changes in physiology and elemental metabolism associated with reproduction

Influence of local antigen exposure dose in the upper respiratory tract on sensitization with cedar pollen

ABSTRACTBackgroundAn increase in Japanese cedar pollen counts is the probable reason for the increase in the number of Japanese cedar hay fever patients. To determine whether local antigen exposure dose affects sensitization with cedar pollen, we compared serum levels of specific IgE antibody in rats exposed to higher and lower doses of cedar pollen antigen through the nose.MethodsSerum levels of cedar pollen-specific IgE antibody was examined in Brown Norway rats exposed to a higher dose of (20 μg) Cry j I, a lower dose (2 μg) of Cry j I or no dose for 6 months. Serum levels of cedar pollen-specific IgE antibody were measured by reverse IgE-capture ELISA. The extent of local eosinophilia in the nasal, laryngeal and tracheal mucosa of rats exposed higher and lower doses of cedar pollen antigen and controls were observed microscopically.ResultsThe mean serum levels of specific IgE antibody in rats exposed to the higher dose were significantly higher than those in rats exposed to the lower dose, and the mean levels in rats in the lower-dose group were significantly higher than in controls. The extent of eosinophilia in the nasal mucosa in the higher-dose group was significantly greater than in controls, but no significant differences between the lower-dose group and controls were found. The extent of eosinophilia in the laryngeal mucosa in the higher-dose group was significantly greater than that in the lower-dose group and in controls. Only a small degree of eosinophilia was observed in the trachea of all three groups.ConclusionsLocal exposure dose of the upper airway to cedar pollen may affect sensitization

Bullous Pemphigoid IgG Induces BP180 Internalization via a Macropinocytic Pathway

Bullous pemphigoid (BP) is an autoimmune blistering skin disease induced by pathogenic autoantibodies against a type II transmembrane protein (BP180, collagen type XVII, or BPAG2). In animal models, BP180 autoantibody-antigen interaction appears insufficient to develop blisters, but involvement of complement and neutrophils is required. However, cultured keratinocytes treated with BP-IgG exhibit a reduction in the adhesive strength and a loss of expression of BP180, suggesting that the autoantibodies directly affect epidermal cell–extracellular matrix integrity. In this study, we explored the consequences of two distinct epithelial cells treated with BP-IgG, particularly the fate of BP180. First, we followed the distribution of green fluorescent protein–tagged BP180 in an epithelial cell line, 804G, and normal human epidermal keratinocytes after autoantibody clustering. After BP-IgG treatment, the adhesive strength of the cells to their substrate was decreased, and BP180 was internalized in both cell types, together with the early endosomal antigen-1. By using various endocytosis inhibitors and a fluid-uptake assay, we demonstrated that BP-IgG–induced BP180 internalization is mediated via a macropinocytic pathway. Moreover, a macropinocytosis inhibitor rescued a BP-IgG–induced reduction in the adhesive strength of the cells from their substrate. The results of this study suggest that BP180 internalization induced by BP-IgG plays an important role in the initiation of disease pathogenesis

Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants

自己集合性ワクチンアジュバントの発見. 京都大学プレスリリース. 2020-10-07.Vaccine ingredients could be hiding in small molecule libraries. 京都大学プレスリリース. 2020-10-07.Immune potentiators, termed adjuvant, trigger early innate immune responses to ensure the generation of robust and long‐lasting adaptive immune responses of vaccines. Here we present study that takes advantage of a self‐assembling small molecule library for the development of a novel vaccine adjuvant. Cell‐based screening of the library and subsequent structural optimization led to the discovery of a simple, chemically tractable deoxycholate derivative (molecule 6 , also named cholicamide) whose well‐defined nano‐assembly potently elicits innate immune responses in macrophages and dendritic cells. Functional and mechanistic analyses indicate that the virus‐like assembly is engulfed inside cells and stimulates the innate immune response through toll‐like receptor 7 (TLR7), an endosomal TLR that detects single‐stranded viral RNA. As an influenza vaccine adjuvant in mice, molecule 6 was as potent as Alum, a clinically used adjuvant. The studies described here paves the way for a new approach to discovering and designing self‐assembling small‐molecule adjuvants against pathogens, including emerging viruses

Calcineurin knockout mice show a selective loss of small spines

Calcineurin is required for long-term depression and activity-dependent spine shrinkage, and calcineurin mutations have been identified in patients with schizophrenia. Moreover, mice with conditional knockout of calcineurin B (CNB-KO) exhibit behavioral abnormalities suggestive of schizophrenia. Changes in the dendritic spines of these mice, however, have not been investigated. We therefore examined the dendritic spines of CNB-KO mice, and observed a significant reduction in small spines and an increase in large spines in the prefrontal and visual cortices. The effect of CNB-KO on the spine sizes was relatively moderate, possibly due to the presence of spontaneous fluctuations (dynamics) in the dendritic spines themselves. Thus, CNB-KO mice showed a spine phenotype similar to those recently reported in patients with schizophrenia

Regulation of PD-L1 expression in non–small cell lung cancer by interleukin-1β

IntroductionProgrammed cell death–ligand 1 (PD-L1) is a biomarker for prediction of the clinical efficacy of immune checkpoint inhibitors in various cancer types. The role of cytokines in regulation of PD-L1 expression in tumor cells has not been fully characterized, however. Here we show that interleukin-1β (IL-1β) plays a key role in regulation of PD-L1 expression in non–small cell lung cancer (NSCLC).MethodsWe performed comprehensive screening of cytokine gene expression in NSCLC tissue using available single-cell RNA-Sequence data. Then we examined the role of IL-1β in vitro to elucidate its induction of PD-L1 on NSCLC cells.ResultsThe IL-1β gene is highly expressed in the tumor microenvironment, particularly in macrophages. The combination of IL-1β and interferon-γ (IFN-γ) induced a synergistic increase in PD-L1 expression in NSCLC cell lines. IL-1β and IFN-γ also cooperatively activated mitogen-activated protein kinase (MAPK) signaling and promoted the binding of downstream transcription factors to the PD-L1 gene promoter. Furthermore, inhibitors of MAPK signaling blocked upregulation of PD-L1 by IL-1β and IFN-γ.DiscussionOur study reports high levels of IL-1β in the tumor microenvironment may cooperate with IFN-γ to induce maximal PD-L1 expression in tumor cells via activation of MAPK signaling, with the IL-1β–MAPK axis being a promising therapeutic target for attenuation of PD-L1–mediated suppression of antitumor immunity