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

Radiolabeling of aromatic compounds using K[*Cl]Cl and OXONE

We report a novel labeling method for the rapid radiochlorination of aromatic compounds using no-carrier-added short half-life radioactive chloride ions ([38,39Cl]Cl-and [34mCl]Cl-) and OXONE (Sigma-Aldrich, Japan) as an oxidation reagent.The reaction of radioactive chloride ions with anisole in the presence of OXONE gave a mixture of p-[*Cl]chloroanisole and o-[*Cl]-chloroanisole, with a radiochemical conversion yield ofmore than 85%(not decay corrected) and selectivity of 7:3,within 10 min. Regioselective radioactive chlorination was achieved by chlorodestannylation of tributylstannyl compounds to afford the corresponding radiochlorinated compounds (p-chloroanisole and m-chloroanisole) in satisfactory radiochemical yields (80–95% and 46–65%, respectively)

Radiosynthesis of [2-11C-carbonyl]dantrolene using [11C]phosgene for PET

Automated radiosynthesis of [2-11C-carbonyl]dantrolene, the substrate of breast cancer resistanceprotein (BCRP/ABCG2), was performed for the first time through a multi-step/one-pot labeling sequencethat started with ethyl 2-{2-[5-(4-nitrophenyl)furfurylidene]hydrazino}acetate and used [11C]phosgeneas a labeling agent. After optimization of the automated synthesis conditions and parameters, [2-11Ccarbonyl]dantrolene was obtained at a radiochemical yield of 34.078.4% (decay-corrected). Theradiochemical purity was greater than 98% and the specific activity was 46.8715.2 GBq/mmol at theend of the synthesis

Simple and effective method for producing [11C]phosgene using an environmental CCl4 gas detection tube

AbstractIntroductionCarbon-11-labeled phosgene is an important labeling precursor for PET molecular probes. Despite the usefulness of [11C]phosgene, some difficulties, especially in the formation of [11C]phosgene process from [11C]CCl4, hamper its use. The present article shows a simple preparation method for [11C]phosgene.Method[11C]CCl4 was obtained using the conventional method by passing a mixture of [11C]CH4 and Cl2 through a heated quartz tube. The [11C]CCl4 was transformed to [11C]phosgene simply by passing through a pretreatment tube of a Kitagawa gas detection system for the working-environmental CCl4 concentration measurement at room temperature with a flow rate of 50 ml/min.ResultThis tube successfully transformed [11C]CCl4 to [11C]phosgene at room temperature. [11C]Phosgene was obtained at nearly 80% radiochemical yield (EOB) in a short synthesis time with high reproducibility.ConclusionA high yield and reliable [11C]phosgene production method using a gas detector tube system for working-environmental CCl4 concentration measurement was developed

RADIOLABELLING OF OLIGOPEPTIDES CONTAINING [1-11C]-1,2,3,4-TETRAHYDRO--CARBOLINE-3-CARBOXYLIC ACID VIA A PICTET-SPENGLER REACTION

第４９回ペプチド討論

Carbon-11 radiolabeling of an oligopeptide containing tryptophan hydrochloride via a Pictet-Spengler reaction using carbon-11 formaldehyde

A procedure for the synthesis of a11C-labeled oligopeptide containing [1-11C]1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid([1-11C]Tpi) from the corresponding Trp•HCl-containing peptides has been developed involving a Pictet-Spengler reactionwith [11C]formaldehyde. The synthesis of [1-11C]Tpi from Trp and [11C]formaldehyde was examined as a model reaction withthe aim of developing a facile and effective method for the labeling of peptides with carbon-11. The Pictet-Spengler reactionof Trp and [11C]formaldehyde in acidic media (TsOH or HCl) afforded the desired [1-11C]Tpi in a moderate radiochemical yield.Herein, the application of a Pictet-Spengler reaction to an aqueous solution of Trp•HCl gave the desired product with aradiochemical yield of 45.2%. The RGD peptide cyclo[Arg-Gly-Asp-D-Tyr-Lys] was then selected as a substrate for the labelingreaction with [11C]formaldehyde. The radiolabeling of a Trp•HCl-containing RGD peptide using the Pictet-Spengler reactionwas successful. Furthermore, the remote-controlled synthesis of a [1-11C]Tpi-containing RGD peptide was attempted by usingan automatic production system to generate [11C]CH3I. The radiochemical yield of the [1-11C]Tpi-containing RGD at the end ofsynthesis (EOS) was 5.9 ± 1.9% (n = 4), for a total synthesis time of about 35 min. The specific activity was 85.7 ± 9.4 GBq/μmolat the EOS. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd

Radiolabeling of Oligopeptides Containing [1-11C]-1,2,3,4-Tetrahydro-β-carborine-3-carboxylic Acid via a Pictet-Spengler Reaction

The synthesis of 11C-labelled peptide, cyclo[Arg-Gly-Asp-D-Tyr-Lys([1-11C]-Tpi)], from corresponding Trp-containing peptides via a Pictet-Spengler reaction by using [11C]formaldehyde is reported. Radiochemical yield of peptide at end of synthesis was 6.3±2.3% with a radiochemical purity of >98%, and the total synthesis time was about 35 min. The specific activity was 75.3±7.8 GBq/mol