High Resolution Continuous Flow Analysis System developed at the Ice Core Research Center National Institute of Polar Research

第6回極域科学シンポジウム[OM] 極域気水圏11月16日（月）　統計数理研究所 セミナー室2（D304

Synthesis of yellow and red fluorescent 1,3a,6a-triazapentalenes and the theoretical investigation of their optical properties

To expand the originally developed fluorescent 1,3a,6a-triazapentalenes as fluorescent labelling reagents, the fluorescence wavelength of the 1,3a,6a-triazapentalenes was extended to the red color region. Based on the noteworthy correlation of the fluorescence wavelength with the inductive effect of the 2-substituent, electron-deficient 2-(2-cyano-4-methoxycarbonylphenyl)-1,3a,6a-triazapentalene and 2-(2,6-dicyano-4-methoxycarbonylphenyl)-1,3a,6a-triazapentalene were synthesized. The former exhibited yellow fluorescence and the latter exhibited red fluorescence, and both compounds exhibited large Stokes shifts, and the 1,3a,6a-triazapentalene system enabled the same fluorescent chromophore to cover the entire region of visible wavelengths. The potential applications of the 1,3a,6a-triazapentalenes as fluorescent probes in the fields of the life sciences were investigated, and the 1,3a,6a-triazapentalene system was clearly proven to be useful as a fluorescent reagent for live cell imaging. Quantum chemical calculations were performed to investigate the optical properties of the 1,3a,6a-triazapentalenes. These calculations revealed that the excitation involves a significant charge-transfer from the 1,3a,6a-triazapentalene skeleton to the 2-substituent. The calculated absorption and fluorescence wavelengths showed a good correlation with the experimental ones, and thus the system could enable the theoretical design of substituents with the desired optical properties

Synthesis and Evaluation of 1,3a,6a-triazapentalene (TAP)-bonded system

A method of synthesizing a directly connected 1,3a,6a-triazapentalene (TAP) ring system as a linearly bonded aromatic system with a planar form was established. Various TAP-dimers and a 2-alkyl-TAP-trimer were synthesized and their fluorescence properties were evaluated. Although the direct connection of the TAP ring with other TAP rings did not affect the fluorescence properties in diluted solvent, TAP-dimers showed unique fluorescence properties derived from the aggregation state under highly concentrated conditions. In particular, TAP-dimer 5f showed aggregation-induced emission in highly concentrated solution, and 5b showed typical mechanochromic fluorescence in the solid state despite their compact molecular size

Epigenetic alterations in sperm associated with male infertility

The most common form of male infertility is a low sperm count, known as oligozoospermia. Studies suggest that oligozoospermia is associated with epigenetic alterations. Epigenetic alterations in sperm, which may arise due to the exposure of gametes to environmental factors or those that pre-exist in the sperm of infertile individuals, may contribute to the increased incidence of normally rare imprinting disorders in babies conceived after assisted reproductive technology using the sperm of infertile men. Genomic imprinting is an important developmental process whereby the allelic activity of certain genes is regulated by DNA methylation established during gametogenesis. The aberrant expression of several imprinted genes has been linked to various diseases, malignant tumors, lifestyle and mental disorders in humans. Understanding how infertility and environmental factors such as reproductive toxicants, certain foods, and drug exposures during gametogenesis contribute to the origins of these disorders via defects in sperm is of paramount importance. In this review, we discuss the association of epigenetic alterations with abnormal spermatogenesis and the evidence that epigenetic processes, including those required for genomic imprinting, may be sensitive to environmental exposures during gametogenesis, fertilization and early embryonic development. In addition, we review imprinting diseases and their relationships with environmental factors. While the plasticity of epigenetic marks may make these more susceptible to modification by the environment, this also suggests that aberrant epigenetic marks may be reversible. A greater understanding of this process and the function of epidrugs may lead to the development of new treatment methods for many adult diseases in the future

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

VERTECS: 6U CubeSat Mission to Study Star-Formation History by Observation of Visible Extragalactic Background Light

We describe an astronomical 6U CubeSat mission VERTECS (Visible Extragalactic background RadiaTion Exploration by CubeSat). The scientific purpose of VERTECS is to reveal star-formation history of the universe by observation of the extragalactic background light (EBL) in visible wavelengths. Earlier observations by sounding rockets and infrared astronomical satellites have shown that the near-infrared EBL is several times brighter than the integrated light of known galaxies. As candidates for the excess light, first-generation stars in the early universe or low-redshift intra-halo light have been proposed, but it has not been concluded. Since these objects are expected to show different emission spectra in visible wavelengths, precise visible observation is important to reveal the origin of excess light. Since detection sensitivity of the EBL is determined by the product of telescope aperture and field of view, a small wide-field telescope system enables the EBL observation with high sensitivity. In VERTECS mission, we develop a 6U CubeSat equipped with a 3U size telescope optimized for observation of visible EBL. The telescope is composed of lens optics and a CMOS sensor of 3k times 3k array format, which is designed to observe the sky in four photometric bands in 400-800nm. The satellite bus is composed of on-board computer (OBC), electric power system (EPS), communication (COM), attitude determination and control system (ACDS), and thermal structure. Design of OBC and EPS is based on heritage of CubeSats developed at Kyushu Institute of Technology, but deployable solar array wings is added to EPS to supply sufficient power to the VERTECS subsystems. In COM system, S-band is used for command uplink and X-band is used for high-speed downlink of large-size images captured by the telescope. Since the EBL measurement need discrimination of the background light from discrete foreground stars, VERTECS requires 10 arcseconds pointing stability (1 sigma) over 1 minute exposure. In 2022, VERTECS was selected for JAXA-Small Satellite Rush Program (JAXA-SMASH Program), a new program that encourages universities, private companies and JAXA to collaborate to realize small satellite missions utilizing commercial small launch opportunities, and to diversify transportation services in Japan. We have been working on functionality and interface teast using Bread Board Model (BBM), and enviroonmental tests by using the satellite structure thermal model. Launch of the satellite is planned in FY2025. We aim at developing the satellite and obtaining scientific results much more quickly than recent large astronomical-satellite missions

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

FE-SEM observation of chains of nanohillocks in SrTiO3 and Nb-doped SrTiO3 surfaces irradiated with swift heavy ions

高速重イオン (SHI) がセラミックスに真上から入射すると、SHI 一つに対してヒロック (ナノメートルサイズの隆起物) が一つ表面に形成される。一方で近年、SHI がチタン酸ストロンチウム (SrTiO3) や酸化チタン (TiO2)の表面をかするように入射した場合、表面にはイオンの飛跡に沿って連続的に複数個のヒロックが形成されると報告がある。これらは原子間力顕微鏡 (AFM) を用いて観察されており、観察結果には AFM のプローブ寸法由来の測定誤差を含んでいる。本研究では、ヒロックのサイズより十分小さい分解能 (1.5 nm) を有し、非接触で観察可能な電界放出形走査電子顕微鏡 (FE-SEM) を用いて連続ヒロックを観察する手法を検討した。本発表では連続ヒロックのFE-SEM観察結果とともに、新しい連続ヒロックの形状変化メカニズムを提案する