RB1CC1 Together with RB1 and p53 Predicts Long-Term Survival in Japanese Breast Cancer Patients

RB1-inducible coiled-coil 1 (RB1CC1) plays a significant role in the enhancement of the retinoblastoma tumor suppressor (RB1) pathway and is involved in breast cancer development. However, RB1CC1's role in clinical progression of breast cancer has not yet been evaluated, so, as a first step, it is necessary to establish its usefulness as a tool to evaluate breast cancer patients. In this report, we have analyzed the correlation between abnormalities in the RB1CC1 pathway and long-term prognosis, because disease-specific death in later periods (>5 years) of the disease is a serious problem in breast cancer. Breast cancer tissues from a large cohort in Japan were evaluated by conventional immunohistochemical methods for the presence of the molecules involved in the RB1CC1 pathway, including RB1CC1, RB1, p53, and other well-known prognostic markers for breast cancer, such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The correlation between the immunohistochemical results and clinical outcomes of 323 breast cancer patients was analyzed using a Kaplan-Meier log-rank test and a multivariate Cox proportional hazards regression analysis. Absence of nuclear RB1CC1 expression was associated with the worst prognosis (Log-rank test, Chi-Square value = 17.462, p<0.0001). Dysfunction of either one of RB1CC1, RB1, or p53 was associated with the highest risk for cancer-specific death, especially related to survival lasting more than 5 years (multivariate Cox proportional hazard ratio = 3.951, 95% Confidence Interval = 1.566–9.967, p = 0.0036). Our present data demonstrate that the combined evaluation of RB1CC1, RB1 and p53 by conventional immunohistochemical analysis provides an accurate prediction of the long-term prognoses of breast cancer patients, which can be carried out as a routine clinical examination

Seasonal variations of NO observed with a microwave radiometer at Syowa Station

第3回極域科学シンポジウム　横断セッション「中層大気・熱圏」 11月26日（月） 国立極地研究所 ２階大会議

2015年の昭和基地でのNOおよびオゾンの地上ミリ波モニタリング観測

第6回極域科学シンポジウム分野横断型セッション：[IM] 横断　中層大気・熱圏11月17日（火）　国立極地研究所１階交流アトリウ

Initial results of mm-wave spectroscopic observation at Syowa Station

第2回極域科学シンポジウム/第35回極域宙空圏シンポジウム 11月15日（火） 国立極地研究所 2階大会議

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

Study of temporal variations of nitric oxide in the mesosphere and lower thermosphere over Syowa station, Antarctica

主論文ファイル公開2015年8月28

Astrometry of 6.7 GHz Methanol Maser toward W3(OH) with Japanese VLBI Network

We present the results of multi-epoch VLBI observations for 6.7 GHz methanol maser emission toward the UC HII region of W3(OH) with Japanese VLBI Network (JVN) [1]. Based on phase-referencing VLBI astrometry, we derived the trigonometric annual parallax to be 0.598 ± 0.067 mas, corresponding to a distance of 1.67 +0.21 kpc. This is the first detection of parallax for a 6.7 GHz methanol maser source with JVN, following European VLBI Network [2], and demonstrates that JVN/VERA is capable of conducting VLBI astrometry for 6.7 GHz methanol maser sources within a few kpc from the Sun. Based on in-beam mapping of the W3(OH) methanol maser, we also measured the internal proper motions of its 6.7 GHz methanol maser for the first time. The internal proper motions basically show north-south expansio

Enhanced Self-Assembly and Mechanical Properties of Cellulose-Based Triblock Copolymers: Comparisons with Amylose-Based Triblock Copolymers

Herein, we compared the microphase-separation behavior and mechanical properties of cellulose- and amylose-based block copolymers (BCPs). Various cellooligosaccharide triacetate-b-poly(delta-decanolactone)-b-cellooligosaccharide triacetates (AcCel(n)-b-PDL-b-AcCel(n)s), which are cellulose-based ABA-type BCPs, with PDL molecular weights of approximately 5, 10, and 20 kg mol(-1) and PDL volume fractions of 0.65, 0.77, and 0.87, were synthesized from alpha,omega-diazido-end-functionalized PDLs and propargyl-end-functionalized cellooligosaccharide triacetates via click chemistry. We adopted the cellodextrin-phosphorylase-mediated oligomerization of alpha-D-glucose-1-phosphase in the presence of a propargyl-end-functionalized cellobiose primer to synthesize the functional cellooligosaccharide segment. The maltooligosaccharide triacetate-b-poly(delta-decanolactone)-b-maltooligosaccharide triacetate (AcMal(n)-b-PDL-b-AcMal(n)s) amylose counterparts were also synthesized in a similar manner. Small-angle X-ray scattering experiments and atomic force microscopy revealed that AcCel(n)-b-PDL-b-AcCel(n)s are more likely to microphase-separate into ordered nanostructures compared to AcMal(n)-b-PDL-b-AcMal(n)s, despite their comparable chemical compositions and molecular weights. Furthermore, AcCel(n)-b-PDL-b-AcCel(n)s exhibited significantly superior mechanical performance compared to their amylose counterparts under tensile testing, with Young's modulus and stress at break of AcCel(n)-b-PDL10k-b-AcCel(n) being 2.3 and 1.8 times higher, respectively, than those of AcMal(n)-b-PDL10k-b-AcMal(n). The enhanced microphase-separation and mechanical properties of AcCel(n)-b-PDL-b-AcCel(n)s were found to be attributable to the stiffness and crystalline nature of the AcCel(n) segments. These results demonstrate the advantages of using cellulose derivatives to synthesize novel biofunctional materials