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

A Case of Dermatomyositis with Esophageal Fistula in Whom Blind Mucosal Biopsy Detected Occult Oropharyngeal Carcinoma

We present a case of anti-transcription intermediary factor 1 (anti-TIF-1) antibody-positive dermatomyositis with concomitant esophageal fistula and extensive truncal erythema. The characteristic cutaneous features and presence of anti-TIF-1 antibodies were predictive for internal malignancy. However, repeated examinations for internal malignancy showed none, and blind mucosal biopsy was needed to diagnose oropharyngeal carcinoma. We should note the possibility of occult nasopharyngeal carcinoma and consider performing blind mucosal biopsy in dermatomyositis with esophageal fistula, especially with extensive truncal erythema

Chlamydomonas reinhardtii Dangeard (Chlamydomonadales, Chlorophyceae) mutant with multiple eyespots

We have isolated a new Chlamydomonas reinhardtii Dangeard (Chlamydomonadales, Chlorophyceae) mutant with from one up to more than four eyespots cell -1. It was designated mes (multiple eyespots)-10. A wild-type cell has a single eyespot, located under the chloroplast envelope, at a certain position near the cell\u27s equator where the chloroplast envelope is in contact with the cell membrane. The eyespot(s) in mes-10, however, are located at various positions on its chloroplast. The mes-10 cells displayed negative phototaxis to 480-500 nm light. This behavior differed from that of a similar mutant, ptx4, which has been shown to have multiple eyespots and display no phototaxis (Pazour et al., J. Cell Biol. 1995; 131: 427-40). Mes-10 may retain a functional photoreceptor and a photosignal transduction system independently of its multiple eyespots. This mutant should be useful for studying how C. reinhardtii responds to light signals, as well as how eyespots are formed in the cell

A novel host shift and invaded range of a seed predator, Acanthoscelides macrophthalmus (Coleoptera: Chrysomelidae: Bruchinae), of an invasive weed, Leucaena leucocephala

An endophagous seed predator, Acanthoscelides macrophthalmus (Coleoptera: Chrysomelidae: Bruchinae), utilizes Neotropical Leucaena (Fabaceae: Mimosoideae). One of its hosts, Leucaena leucocephala, is a fast-growing nitrogen-fixing tree that serves as a multipurpose beneficial plant but eventually becomes an aggressive invader where it was introduced. Herein, we report A. macrophthalmus invasion of the Far East, South Asian tropics and subtropics (Japanese Pacific Islands, Taiwan, Southern China, Northern Thailand and Southern India). Of other field-collected mimosoid legumes, an introduced tree, Falcataria moluccana, in Taiwan was found to be used by the seed predator. Conversely, our published work review revealed that the seed predator had retained high host specificity to Leucaena species in its native and introduced regions. Acanthoscelides macrophthalmus was able to utilize aphagously postharvest mature seeds for oviposition and larval development, which is a trait of post-dispersal seed predators. We confirmed that A. macrophthalmus that was reared on L. leucocephala was able to utilize F. moluccana as well. Although the relatively high host specificity of the oligophagous beetle is suitable for controlling the weedy L. leucocephala, the potential host range expansion confirmed by this study must be cautioned