The first Japanese biobank of patient‐derived pediatric acute lymphoblastic leukemia xenograft models

A lack of practical resources in Japan has limited preclinical discovery and testing of therapies for pediatric relapsed and refractory acute lymphoblastic leukemia (ALL), which has poor outcomes. Here, we established 57 patient-derived xenografts (PDXs) in NOD.Cg-Prkdcscidll2rgtm1Sug/ShiJic (NOG) mice and created a biobank by preserving PDX cells including three extramedullary relapsed ALL PDXs. We demonstrated that our PDX mice and PDX cells mimicked the biological features of relapsed ALL and that PDX models reproduced treatment-mediated clonal selection. Our PDX biobank is a useful scientific resource for capturing drug sensitivity features of pediatric patients with ALL, providing an essential tool for the development of targeted therapies

Photometry and Polarimetry of 2010 XC15_{15}: Observational Confirmation of E-type Near-Earth Asteroid Pair

Asteroid systems such as binaries and pairs are indicative of physical properties and dynamical histories of the Small Solar System Bodies. Although numerous observational and theoretical studies have been carried out, the formation mechanism of asteroid pairs is still unclear, especially for near-Earth asteroid (NEA) pairs. We conducted a series of optical photometric and polarimetric observations of a small NEA 2010 XC$_{15}$ in 2022 December to investigate its surface properties. The rotation period of 2010 XC$_{15}$ is possibly a few to several dozen hours and color indices of 2010 XC$_{15}$ are derived as $g-r=0.435\pm0.008$, $r-i=0.158\pm0.017$, and $r-z=0.186\pm0.009$ in the Pan-STARRS system. The linear polarization degrees of 2010 XC$_{15}$ are a few percent at the phase angle range of 58$^{\circ}$ to 114$^{\circ}$. We found that 2010 XC$_{15}$ is a rare E-type NEA on the basis of its photometric and polarimetric properties. Taking the similarity of not only physical properties but also dynamical integrals and the rarity of E-type NEAs into account, we suppose that 2010 XC$_{15}$ and 1998 WT$_{24}$ are of common origin (i.e., asteroid pair). These two NEAs are the sixth NEA pair and first E-type NEA pair ever confirmed, possibly formed by rotational fission. We conjecture that the parent body of 2010 XC$_{15}$ and 1998 WT$_{24}$ was transported from the main-belt through the $\nu_6$ resonance or Hungaria region.Comment: Resubmitted to AAS Journals. Any comments are welcom

Thermal Infrared Imaging Experiments of C-Type Asteroid 162173 Ryugu on Hayabusa2

The thermal infrared imager TIR onboard Hayabusa2 has been developed to investigate thermo-physical properties of C-type, near-Earth asteroid 162173 Ryugu. TIR is one of the remote science instruments on Hayabusa2 designed to understand the nature of a volatile-rich solar system small body, but it also has significant mission objectives to provide information on surface physical properties and conditions for sampling site selection as well as the assessment of safe landing operations. TIR is based on a two-dimensional uncooled micro-bolometer array inherited from the Longwave Infrared Camera LIR on Akatsuki (Fukuhara et al., 2011). TIR takes images of thermal infrared emission in 8 to 12 μm with a field of view of 16×12∘ and a spatial resolution of 0.05∘ per pixel. TIR covers the temperature range from 150 to 460 K, including the well calibrated range from 230 to 420 K. Temperature accuracy is within 2 K or better for summed images, and the relative accuracy or noise equivalent temperature difference (NETD) at each of pixels is 0.4 K or lower for the well-calibrated temperature range. TIR takes a couple of images with shutter open and closed, the corresponding dark frame, and provides a true thermal image by dark frame subtraction. Data processing involves summation of multiple images, image processing including the StarPixel compression (Hihara et al., 2014), and transfer to the data recorder in the spacecraft digital electronics (DE). We report the scientific and mission objectives of TIR, the requirements and constraints for the instrument specifications, the designed instrumentation and the pre-flight and in-flight performances of TIR, as well as its observation plan during the Hayabusa2 mission

Video Observations of Tiny Near-Earth Objects with Tomo-e Gozen

We report the results of video observations of tiny (diameter less than 100 m) near-Earth objects (NEOs) with Tomo-e Gozen on the Kiso 105 cm Schmidt telescope. A rotational period of a tiny asteroid reflects its dynamical history and physical properties since smaller objects are sensitive to the YORP effect. We carried out video observations of 60 tiny NEOs at 2 fps from 2018 to 2021 and successfully derived the rotational periods and axial ratios of 32 NEOs including 13 fast rotators with rotational periods less than 60 s. The fastest rotator found during our survey is 2020 HS7 with a rotational period of 2.99 s. We statistically confirmed that there is a certain number of tiny fast rotators in the NEO population, which have been missed with any previous surveys. We have discovered that the distribution of the tiny NEOs in a diameter and rotational period (D-P) diagram is truncated around a period of 10 s. The truncation with a flat-top shape is not explained well either by a realistic tensile strength of NEOs or suppression of YORP by meteoroid impacts. We propose that the dependence of the tangential YORP effect on the rotational period potentially explains the observed pattern in the D-P diagram.Comment: This article is published in PASJ as open access, published by OUP (https://doi.org/10.1093/pasj/psac043). 27 pages, 16 figure

Highly porous nature of a primitive asteroid revealed by thermal imaging

Carbonaceous (C-type) asteroids are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth’s atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR) onboard the spacecraft Hayabusa2, indicating that the asteroid’s boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m−2 s−0.5 K−1 (300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect. We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites. These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies.Additional co-authors: Tsuneo Matsunaga, Takeshi Imamura, Takehiko Wada, Sunao Hasegawa, Jörn Helbert, Thomas G. Müller, Jens Biele, Matthias Grott, Maximilian Hamm, Marco Delbo, Naru Hirata, Naoyuki Hirata, Yukio Yamamoto, Seiji Sugita, Noriyuki Namiki, Kohei Kitazato, Masahiko Arakawa, Shogo Tachibana, Hitoshi Ikeda, Masateru Ishiguro, Koji Wada, Chikatoshi Honda, Rie Honda, Yoshiaki Ishihara, Koji Matsumoto, Moe Matsuoka, Tatsuhiro Michikami, Akira Miura, Tomokatsu Morota, Hirotomo Noda, Rina Noguchi, Kazunori Ogawa, Kei Shirai, Eri Tatsumi, Hikaru Yabuta, Yasuhiro Yokota, Manabu Yamada, Masanao Abe, Masahiko Hayakawa, Takahiro Iwata, Masanobu Ozaki, Hajime Yano, Satoshi Hosoda, Osamu Mori, Hirotaka Sawada, Takanobu Shimada, Hiroshi Takeuchi, Ryudo Tsukizaki, Atsushi Fujii, Chikako Hirose, Shota Kikuchi, Yuya Mimasu, Naoko Ogawa, Go Ono, Tadateru Takahashi, Yuto Takei, Tomohiro Yamaguchi, Kent Yoshikawa, Fuyuto Terui, Takanao Saiki, Satoru Nakazawa, Makoto Yoshikawa, Seiichiro Watanabe & Yuichi Tsud

Maturation-associated changes in toxicity of the pufferfish Takifugu poecilonotus.

From October 2006 to December 2007, wild specimens of the pufferfish Takifugu poecilonotus (93 females, 45 males) were collected from the Ariake Sea. Tissue toxicity was examined by mouse bioassay, and tetrodotoxin (TTX) content in the blood plasma by enzyme-linked immunosorbent assay. The relationship between toxicity and maturation was investigated based on changes in the gonadosomatic index: December-March in females and November-March in males, the \u27maturation period\u27; April, \u27just after spawning\u27; and the other months, the \u27ordinary period\u27. Toxicity of both sexes was high throughout the year, but sharply declined in April. In all tissues examined (skin, liver, and ovary) other than testis, toxicity exceeded 1000MU/g or 10,000MU/individual in many individuals. Seasonal profiles of tissue toxicity differed markedly between sexes. In females, liver toxicity was high during the ordinary period, and ovary toxicity was high during the maturation period. In males, little maturation-associated change in the toxin distribution was observed. Plasma TTX levels were similar between the sexes (1.59-15.1MU/ml), and fluctuated largely throughout the year without corresponding changes in tissue toxicity. The percentage of TTX binding to high molecular-weight substances in the plasma varied in association with maturation; the binding ratio fluctuated at relatively low levels during the ordinary period, and stabilized at a high level during the maturation period

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