VEGF Polymorphism rs3025039 and Human T-Cell Leukemia Virus 1 (HTLV-1) Infection among Older Japanese Individuals: A Cross-Sectional Study

Previous studies have reported a close correlation between vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, and human T-cell leukemia virus 1 (HTLV-1). However, an association between genetic characteristics related to VEGF and HTLV-1 infection has not yet been reported. Because the VEGF polymorphism rs3025039 is inversely associated with serum concentrations of VEGF, we focus on rs3025039 in the present study. To clarify the association between the VEGF polymorphism rs3025039 and HTLV-1 infection, a cross-sectional study of 1924 Japanese individuals aged 60–79 years who participated in general health check-ups was conducted. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for HTLV-1 infection in relation to rs3025039 genotype were calculated with adjustment for known confounders. Compared with rs3025039 CC-homozygotes, (T) allele carriers had a significantly lower OR for HTLV-1 infection. The adjusted OR and 95% CI for HTLV-1 infection was 0.70 (0.54–0.91) (p = 0.009). Genetic characteristics related to lower angiogenesis activity might be associated with a lower chance of establishing HTLV-1 infection. Although further investigation is necessary, angiogenesis might play a crucial role in the establishment of HTLV-1 infection

新規保健事業の成果を高めるために市町村保健師が必要と認識する職場環境

Purpose: The purpose of this study was to identify aspects of the work environment that public health nurses and other health professionals who had conducted new public health projects and achieved favorable outcomes, considered necessary to help them achieve their success. Methods: Participants of this qualitative descriptive study were ３７ public health nurses and one nutritionist working for municipalities, who had been engaged in research projects. They were divided into six groups for focus group discussions facilitated by an interview guide. Qualitative descriptive analysis focused on data relating to the work environments which were considered necessary to achieve favorable outcomes and were successfully put in place or those which failed to be in place despite their consideration. Results: The work environments the public health nurses and other health professionals considered necessary to improve the outcomes of new public health projects were divided into five categories and １5 subcategories. The categories included “OJT to meet new needs for learning,” “framework for adequate management of duties to reduce individual workloads,” “equipment or system to enable easy access of key information,” “a workplace culture that facilitates mutual understanding,” and “collaboration/cooperation-oriented workplace with a positive and friendly atmosphere.” Discussion: The results indicate that the work environments necessary to further improve the outcomes can generally be divided into two types: work environments that fit the characteristics of a new project on an ad-hoc basis when it is introduced, and work environments that should routinely already be in place. This suggests the necessity of having close communication among public health nurses and workplaces not only when a new project is introduced but also on a routine basis. From now on, we need to identify work environments that are particularly difficult for public health nurses and other health professionals to put in place, and investigate the roles of public health nurse supervisors and managers

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

Allelopathy and Allelochemicals of <i>Solidago canadensis</i> L. and <i>S. altissima</i> L. for Their Naturalization

Solidago canadensis L. and Solidago altissima L. are native to North America and have naturalized many other continents including Europa and Asia. Their species is an aggressive colonizer and forms thick monospecific stands. The evidence of the allelopathy for S. canadensis and S. altissima has accumulated in the literature since the late 20th century. The root exudates, extracts, essential oil and rhizosphere soil of S. canadensis suppressed the germination, growth and the arbuscular mycorrhizal colonization of several plants, including native plant species. Allelochemicals such as fatty acids, terpenes, flavonoids, polyphenols and their related compounds were identified in the extracts and essential oil of S. canadensis. The concentrations of total phenolics, total flavonoids and total saponins in the rhizosphere soil of S. canadensis obtained from the invasive ranges were greater than those from the native ranges. Allelochemicals such as terpenes, flavonoids, polyacetylene and phenols were also identified in the extracts, essential oil and the rhizosphere soil in S. altissima. Among the identified allelochemicals of S. altissima, the cis-dehydromatricaria ester may be involved in the allelopathy considering its growth inhibitory activity and its concentration in the rhizosphere soil. Therefore, the allelopathy of S. canadensis and S. altissima may support their invasiveness, naturalization and formation of thick monospecific stands. This is the first review article focusing on the allelopathy of both of S. canadensis and S. altissima

Evolution of the Secondary Metabolites in Invasive Plant Species Chromolaena odorata for the Defense and Allelopathic Functions

Chromolaena odorata (L.) R.M. King &amp; H. Robinson is native to tropical America, and has naturalized in many other countries in tropical Asia, Austria, and West Africa. The species often forms dense thickets and reduces the native species diversity and population in the invasive ranges. The species is also considered as a noxious weed in agriculture fields, and listed in the 100 of the world&rsquo;s worst invasive alien species. The characteristics of its life-history such as the seed production rate, growth pattern, and adaptative ability to the environmental conditions may contribute to the invasiveness of the species. Possible evidence of the defense capacity against the natural enemy, and the allelopathic potential against the competitive plant species for C. odorata has been accumulated in the literature over three decades. The extracts, residues, and/or rhizosphere soil of C. odorata increased the mortality of various insects and parasitic nematodes, and decreased their population. The extracts, residues, and/or rhizosphere soil of C. odorata also inhibited the germination and growth of several plant species including the indigenous plant species in the invasive ranges of C. odorata. Toxic substances, pyrrolizidine alkaloids were found in the leaves and flowers of C. odorata. These pyrrolizidine alkaloids may work as the defense agents against the natural enemies. Several potential allelochemicals such as flavonoids, phenolic acids, and terpenoids were also found in the plant extracts of C. odorata. Some of these compounds may work as allelopathic agents of C. odorata and inhibit the germination and growth of the competitive plant species. These characteristics of C. odorata for the defense function against their natural enemies such as insects and parasitic nematodes, and allelopathic potential against the competitive native plant species may contribute to the invasiveness and naturalization of C. odorata in the new habitats as invasive plant species. However, it is necessary to determine the concentration of these allelochemicals in the neighboring environment of C. odorata such as the rhizosphere soil since allelochemicals are able to work only when they are released into the neighboring environment. It is the first review article focusing on the defense function and allelopathy of C. odorata