Sutimlimab suppresses SARS-CoV-2 mRNA vaccine-induced hemolytic crisis in a patient with cold agglutinin disease

Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2 infection. Sutimlimab is a monoclonal antibody that inhibits the classical complement pathway of the C1s protein and shows rapid and sustained inhibition of hemolysis in patients with CAD. However, whether sutimlimab could also inhibit hemolysis caused by SARS-CoV-2 mRNA vaccination is uncertain. Here, we present the case of a 70-year-old man with CAD who repeatedly experienced a hemolytic crisis after receiving SARS-CoV-2 mRNA vaccines. The patient eventually underwent SARS-CoV-2 mRNA vaccination safely, without hemolytic attack, under classical pathway inhibition therapy with sutimlimab. This report suggests that appropriate sutimlimab administration can suppress SARS-CoV-2 mRNA vaccination-induced CAD exacerbation, and that it could be a preventive strategy to minimize hemolytic attacks in susceptible populations

Sol-gel chemistry mediated Zn/Al-based complex dispersant for SWCNT in water without foam formation

We report a bimetallic Zn/Al complex as an efficient inorganic dispersant for SWCNT, synthesized from Zn(CH3COO)(2) and Al(NO3)(3). The Zn/Al complex shows more than four times greater efficiency at dispersing SWCNT than widely used surfactants (CTAB and SDS). Besides remarkable dispersibility, the Zn/Al complex does not foam upon any shaking treatment and it can be used just after quick dissolution of the powdered form, which is a marked advantage over surfactants. The Zn/Al complex, containing amorphous Al(CH3COO)(3) and a complex of Zn2+ and NO3- ions, should have a unique dispersion mechanism, differing from the surfactants. Al(CH3COO)(3) has higher affinity for SWCNT than ions, adsorbing onto its surface in the first layer and attracting Zn2+ and NO3- ions. Charge transfer interactions between the Zn/Al complex and SWCNT, as evidenced by optical absorption spectroscopy, should induce a charge on SWCNT; the zeta potential of such coated SWCNT was +55 mV, indicating a high dispersion stability in aqueous media. Hence, the Zn/Al complex can widen the applications of SWCNT to various technologies such as the transparent and conductive films, as well as high performance composite polymers. (C) 2015 Elsevier Ltd. All rights reserved.ArticleCARBON. 94:518-523 (2015)journal articl

Sol–gel chemistry mediated Zn/Al-based complex dispersant for SWCNT in water without foam formation

We report a bimetallic Zn/Al complex as an efficient inorganic dispersant for SWCNT, synthesized from Zn(CH3COO)(2) and Al(NO3)(3). The Zn/Al complex shows more than four times greater efficiency at dispersing SWCNT than widely used surfactants (CTAB and SDS). Besides remarkable dispersibility, the Zn/Al complex does not foam upon any shaking treatment and it can be used just after quick dissolution of the powdered form, which is a marked advantage over surfactants. The Zn/Al complex, containing amorphous Al(CH3COO)(3) and a complex of Zn2+ and NO3- ions, should have a unique dispersion mechanism, differing from the surfactants. Al(CH3COO)(3) has higher affinity for SWCNT than ions, adsorbing onto its surface in the first layer and attracting Zn2+ and NO3- ions. Charge transfer interactions between the Zn/Al complex and SWCNT, as evidenced by optical absorption spectroscopy, should induce a charge on SWCNT; the zeta potential of such coated SWCNT was +55 mV, indicating a high dispersion stability in aqueous media. Hence, the Zn/Al complex can widen the applications of SWCNT to various technologies such as the transparent and conductive films, as well as high performance composite polymers. (C) 2015 Elsevier Ltd. All rights reserved.ArticleCARBON. 94:518-523 (2015)journal articl

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

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