Fine-scale behavioral analysis of the Greenland shark using 3-axis accelerometers

The Tenth Symposium on Polar Science/Ordinary sessions : [OB] Polar Biology, Wed. 4 Dec. / Entrance Hall (1st floor) , National Institute of Polar Researc

エミシズマブは凝固第VIII因子と同様にフィブリン構造およびその安定性を向上させる

Introduction: Emicizumab is an antifactor (F)IXa/FX bispecific antibody, mimicking FVIIIa cofactor function. Emi prophylaxis effectively reduces bleeding events in patients with haemophilia A. The physical properties of emicizumab-induced fibrin clots remain to be investigated, however. Aim: We have investigated the stability and structure of emicizumab-induced fibrin clots. Methods: Coagulation was initiated by activated partial thromboplastin time (aPTT) trigger and prothrombin time (PT)/aPTT-mixed trigger in FVIII-deficient plasma with various concentrations of emicizumab or recombinant FVIII. The turbidity and stability of fibrin clots were assessed by clot waveform and clot-fibrinolysis waveform analyses, respectively. The resulting fibrin was analysed by scanning electron microscopy (SEM). Results: Using an aPTT trigger, the turbidity was decreased and the fibrinolysis times were prolonged in the presence of emicizumab dose-dependently. Scanning electron microscopy imaging demonstrated that emicizumab improved the structure of fibrin network with thinner fibres than in its absence. Although emicizumab shortened the aPTT dramatically, the nature of emicizumab-induced fibrin clots did not reflect the hypercoagulable state. Similarly, using a PT/aPTT-mixed trigger that could evaluate potential emicizumab activity, emicizumab improved the stability and structure of fibrin clot in a series of experiments. In this circumstance, fibrin clot properties with emicizumab at 50 and 100 µg/mL appeared to be comparable to those with FVIII at ~12 and ~24-32 IU/dL, respectively. Conclusion: Emicizumab effectively improved fibrin clot stability and structure in FVIII-deficient plasma, and the physical properties of emicizumab-induced fibrin clots were similar to those with FVIII.博士（医学）・甲第787号・令和3年3月15日© 2020 John Wiley & Sons Ltd.This is the peer reviewed version of the following article: https://onlinelibrary.wiley.com/doi/10.1111/hae.13961, which has been published in final form at https://doi.org/10.1111/hae.13961. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

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

Association of Single Nucleotide Polymorphisms in <i>STAT3</i>, <i>ABCB1</i>, and <i>ABCG2</i> with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients

Signal transducer and activator of transcription (STAT) 3 is a key factor in homeostasis of the oral mucosa by regulating the production of inflammatory cytokines. Sunitinib is a substrate of P-glycoprotein (multidrug resistance (MDR)-1/ABCB1) and breast-cancer resistance protein (BCRP/ABCG2). In this retrospective study, we evaluated the association between sunitinib-induced stomatitis and STAT3, ABCB1, and ABCG2 polymorphisms in patients with metastatic renal cell carcinoma (mRCC). Fifty-two Japanese patients with RCC treated with sunitinib were retrospectively genotyped to elucidate a potential association between STAT3, ABCB1, and ABCG2 polymorphisms and stomatitis development. Stomatitis occurred in 22 out of 52 patients. The TT+TC genotypes at STAT3 rs744166 had an odds ratio of 5.00 against CC genotype for the stomatitis development (95% confident interval, 0.97-25.8). In the Kaplan-Meier method for the cumulative incidence of stomatitis, a statistically significant difference was observed between the TT+TC and CC genotypes in STAT3 rs744166 (p=0.037). Both multiple logistic regression analysis and Cox proportional-hazards regression analysis show STAT3 rs744166 TT+TC genotypes and serum creatinine in each patient were significant independent factors for stomatitis development. In conclusion, STAT3 polymorphism may be a novel risk factor for sunitinib-induced stomatitis in patients with mRCC

Criterion-related validity of Bedriddenness Rank with other established objective scales of ADLs, and Cognitive Function Score with those of cognitive impairment, both are easy-to-use official Japanese scales: A prospective observational study.

AimBedriddenness Rank (BR) and Cognitive Function Score (CFS), issued by the Ministry of Health, Labour and Welfare, Japan, are easy-to-use and widely used in the medical and long-term care insurance systems in Japan. This study aims to clarify the criterion-related validity of the CFS with the Mini-Mental State Examination (MMSE) and ABC Dementia Scale (ABC-DS), and to re-evaluate the criterion-related validity of BR with the Barthel Index (BI) or Katz Index (KI) in more appropriate settings and a larger population compared with the previous study.MethodsA single-center prospective observational study was conducted in an acute care hospital in a suburban city in Japan. All inpatients aged 20 years or older admitted from October 1, 2018 to September 30, 2019. The relationship between BR and the BI and KI, and the relationship between CFS and the MMSE and ABC-DS were analyzed using Spearman's correlation coefficients.ResultsWe enrolled 3,003 patients. Of these, 1,664 (56%) patients exhibited normal BR. The median (interquartile range) values of the BI and KI were 100 (65-100) and 6 (2-6), respectively. Spearman's rank correlation coefficients between BR and the BI and KI were -0.891 (p &lt; 0.001) and -0.877 (p &lt; 0.001), respectively. Of the patients, 1,967 (65.5%) showed normal CFS. The median (interquartile range) MMSE of 951 patients with abnormal CFS and ABC-DS of all patients were 15 (2-21) and 117 (102-117), respectively. Spearman's rank correlation coefficients between CFS and MMSE and ABC-DS were -0.546 (p &lt; 0.001) and -0.862 (p &lt; 0.001), respectively.ConclusionsBR and CFS showed significant criterion-related validity with well-established but complicated objective scales for assessing activities of daily living and cognitive functions, respectively. These two scales, which are easy to assess, are reliable and useful in busy clinical practice or large-scale screening settings