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

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

The Palatability and Physicochemical Properties of Milled Rice for Each Grain-Thickness Group

We examined the palatability and physicochemical properties of milled rice for each grain-thickness group, and examined the influence of physicochemical properties on the grain-thickness-dependent differences of the evaluation of palatability. The thicker the grain, the higher the palatability. However, the palatability of the grains thicker than 2.0 mm did not vary with the grain thickness. For the grains thinner than 2.0 mm, the thinner the grain, the lower the evaluated value of palatability, and the palatability values were very low in the grains thinner than 1.9 mm. The thinner the grain, the higher the protein content. On the contrary, the thinner the grain, the lower the amylose content. The maximum viscosity and breakdown values in angiographic characteristics decreased with decreasing grain thickness. Hardness/adhesion (H/-H) ratio in textural characteristics tended to increase with decreasing grain thickness. The palatability of the cooked rice grains in each grain-thickness group showed a negative correlation with the protein content and H/-H ratio, and strong positive correlation with the amylose content and maximum viscosity. These results indicate that the lowering of palatability with decreasing grain thickness is due to the increase in protein content, the decrease in amylose content, and the decrease in amylographic and textural characteristics. The standard partial regression coefficients against palatability were the highest for the maximum viscosity in Koshihikari, for H/-H ratio in Nipponbare and for protein content in Hinohikari. Thus, in rice cultivated under a certain cultivation condition, physicochemical factors involved in the grain-thickness-dependent difference of palatability are suggested to vary with the cultivar

Confirmation of the Productivity of the Stored Seeds of Wheat and Two-Rowed Barley

To confirm the excellence in productivity of the stored seeds of wheat and two-rowed barley, we examined the growth characters and productivity of the plants developed from the seeds stored at 5°C and 40% relative humidity for various periods but showed a 80% or higher germination percentage, in comparison with those of newly harvested seeds (new seeds). The cultivars of stored seeds were identified by the random amplified polymorphic DNA (RAPD) method. There were no differences in the morphological characters of the seedlings 3 months after emergence between the new seeds and the old seeds (stored for 2 years and 5 months) or the very old seeds (stored for 10 years and 5 months or 16 years and 5 months). On the other hand, there was a positive correlation between the top dry weight at 3 months after emergence and 1,000-grain weight of the seed. In the plants from the old seeds, no significant differences from those from new seeds were observed either in the mean heading date, maturing date, culm lengths, ear length, yield components, grain yield or inspection-grade. On the other hand, in the plants from the very old seeds, the mean heading date, maturing date, culm lengths, yield components and grain yield were significantly different from those in the new seeds in some cultivars. The results of RAPD analysis showed that the band pattern of the very old seeds was the same as that of the new seed in each cultivar. We concluded that the seeds of wheat and two-rowed barley stored for 2 years and 5 months with a germination percentage of higher than 80% are practically useful, showing normal growth characters and productivity. However, it should be noted that some cultivars had inferior grain yield after the seed storage for over 10 years

An Efficient Method for Evaluating the Palatability Deterioration During Storage in Rice

This study was conducted to establish an efficient selection method for breeding highly palatable rice cultivars with less deterioration in palatability during storage. The palatability of the rice stored at room temperature for one yr (old rice) negatively and significantly correlated with the content of free fatty acids in the polished rice and the hardness/adhesion ratio (H/-H ratio) of the cooked rice. Thus, we examined the correlation coefficients of the content of free fatty acids and the H/-H ratio for the old rice and rice stored in a stability-testing chamber (STC) kept at 40°C and relative humidity of 95% for various periods (10, 20, 30 and 60 d). The highest correlation coefficient was observed between the values in the old rice and those in the rice stored in the STC for 30 d. The palatability of the old rice did not correlate with the content of free fatty acids after a 30-d stored in the STC, but negatively and significantly correlated with the H/-H ratio after a 30 d stored in the STC. These results show that we can efficiently evaluate the palatability deterioration during storage in rice by measuring the H/-H ratio of the cooked rice after the stored in the STC for 30 d. The content of the free fatty acids is an effective indicator of palatability deterioration in the old rice, but that in the rice stored in the STC for 30 d is not

A change in electrographic activity and blood flow during interictal and postictal psychotic states in a patient with epilepsy

We report a patient with epilepsy who experienced interictal and postictal psychoses. Her psychiatric symptoms consisted of grandiose and fantastic delusions during both psychotic states. During remission, electroencephalography showed bitemporal epileptiform discharges that were predominant in the right temporal region. Epileptiform discharges present during the psychotic states were predominant in the left temporal region. Single-photon emission computed tomography showed hyperperfusion in the left basal ganglia during the interictal psychotic state and hyperperfusion in the right temporal lobe and left basal ganglia during the postictal psychotic state. We suggest that the occurrence of postictal and interictal psychotic states in this patient were associated with a common change in electrographic activity and blood flow