ピオグリタゾン トウヨ ニヨル フクブ ダイドウミャクリュウ ニオケル コウドウミャク コウカ サヨウ

Accumulating evidence suggests that inflammatory cytokines secreted from visceral fat tissues potentially promote atherosclerosis progression. Recent reports suggested that pioglitazone, which is an anti-diabetes drug, reduces expression of tumor necrosis factor（TNF）‐α and ameliorates insulin-resistance in diabetic mice. Pioglitazone was also reported to suppress progression of coronary atherosclerosis. The objective of this study is to assess the effect of pioglitazone on inflammatory changes in abdominal aortic aneurysms（AAAs）. This study protocol was approved by the medical ethics committee in Tokushima University Hospital. Patients with AAA were randomized into two groups. One was with pioglitazone（Group P）. The other was without pioglitazone（Group C）. Biopsy specimens were obtained from the abdominal subcutaneous fat, the greater omentum, the retroperitoneal periaortic fat and the aneurysmal wall. Immunohistochemistry of CD ６８in those specimens was performed. The number of macrophages in Group P was lower than that in Group C. Expressions of inflammatory cytokines in those specimens were evaluated by real-time quantitative reverse transcription-polymerase chain reaction analysis. Expression of inflammatory cytokines in Group P were reduced, when compaird with those in Group C. Our data may suggest that pioglitazone reduce inflammatory changes in human aortic aneurysm

Enhancement of protein production via the strong DIT1 terminator and two RNA-binding proteins in Saccharomyces cerevisiae

Post-transcriptional upregulation is an effective way to increase the expression of transgenes and thus maximize the yields of target chemicals from metabolically engineered organisms. Refractory elements in the 3′ untranslated region (UTR) that increase mRNA half-life might be available. In Saccharomyces cerevisiae, several terminator regions have shown activity in increasing the production of proteins by upstream coding genes; among these terminators the DIT1 terminator has the highest activity. Here, we found in Saccharomyces cerevisiae that two resident trans-acting RNA-binding proteins (Nab6p and Pap1p) enhance the activity of the DIT1 terminator through the cis element GUUCG/U within the 3′-UTR. These two RNA-binding proteins could upregulate a battery of cell-wall–related genes. Mutagenesis of the DIT1 terminator improved its activity by a maximum of 500% of that of the standard PGK1 terminator. Further understanding and improvement of this system will facilitate inexpensive and stable production of complicated organism-derived drugs worldwide

eDNA metabarcoding analysis reveals the consequence of creating ecosystem‐scale refugia from deer grazing for the soil microbial communities

シカの森林被害は土壌微生物にも波及する --大規模生態系操作実験と環境DNA分析の融合--. 京都大学プレスリリース. 2023-12-22.Ungulate overbrowsing is a growing problem in forests worldwide due to its prolonged and pervasive impact on plant biodiversity and ecosystem functioning. It has been shown that overbrowsing not only reduces plant species diversity and biomass (i.e., direct effects) but also causes a loss of associated trophic levels that could potentially feedback to influence plant community structure (i.e., indirect effects). One of the primary pathways of such indirect effects that have not been fully examined is the impact of overbrowsing on soil microorganisms. Recent studies have shown that soil microorganisms maintain vegetation diversity and drive succession, so it is of critical importance to understand how soil microbial communities might be affected by or protected from the deer impact. To assess the consequence of creating artificial grazing refugia on the structure and composition of soil microbial communities, we compared the distribution and abundance of soil microbial taxa (bacteria, archaea, fungi) at the fenced versus unfenced control sites in the context of a catchment-scale field experiment in Japan. The eDNA metabarcoding analysis of soil microbial communities showed that the numbers of archaea and basidiomycetes fungal species were greater in the fenced site than in the control, while no such pattern was found for bacteria and ascomycetes fungi. Despite the lack of significant influence of the fence treatment on taxonomic composition in the soil fungal communities, their functional guild composition was influenced by the fenced treatment, with significant changes in the abundance of animal pathogens. Thus, although the effect of fencing on soil microbial communities is characterized by complex responses that vary from taxon to taxon, our work suggests that creating ecosystem-scale refugia from deer overgrazing might help sustain certain, if not all, taxa of soil microbial communities

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