55 research outputs found

    Evolutionary Relationships in the Drosophila ananassae Species Cluster Based on Introns of Multiple Nuclear Loci

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    The Drosophila ananassae species cluster includes D. ananassae, D. pallidosa, D. parapallidosa, and the cryptic species “pallidosa-like”, “pallidosa-like Wau” and “papuensis-like” Some of the taxa are sympatric in the South Pacific, Papua New Guinea, and Southeast Asia, and gene flow between different taxa has been suspected for a handful of genes. In the present analysis, we examined DNA sequences of introns in four loci: alpha actinin (Actn) on XL, white (w) on XR, CG7785 on 2L, and zinc ion transmembrane transporter 63C (ZnT63C) on 2R. Phylogenetic trees (neighbor-joining and haplotype network) were inconsistent among these loci. Some haplotypes shared between taxa were found for w, CG7785, and ZnT63C, suggesting recent gene flow. However, no haplotypes were shared, for example, between D. ananassae and D. pallidosa for CG7785, which is close to the proximal breakpoint of In(2L)D. This suggests that taxon-specific inversions prevent gene flow, as predicted by the chromosomal speciation hypothesis

    Therapeutic Effect of Anti-TNF-α Antibody and Levofloxacin(LVFX)in a Mouse Model of Enterohemorrhagic Escherichia coli O157 Infection

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    マウスに腸管出血性大腸菌O157を感染させ、抗TNF-α抗体投与による感染防御効果を調べた。抗TNF-α抗体単独投与群では感染による症状の発現及び組織学的な変化は観察されなかったが、糞便中に少量のO157が証明された。本抗体にLVFXを併用した場合には糞便中のO157は完全に除去されたので、両者の併用により良好な治療結果が得られると考える

    DOCK2 is involved in the host genetics and biology of severe COVID-19

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    「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

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    「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

    ANALYTICAL SCIENCES 2001, VOL.17 SUPPLEMENT i1295 Direct Determination of Tin in Human Hair by Graphite Furnace Atomic Absorption Spectrometry Using Air Ashing in Graphite Tube

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    Direct determination of tin in human hair was performed by graphite furnace atomic absorption spectrometry. Human hair was cut into 3-5 mm long and 1-2 mg of the sample was directly introduced into a pyrolytically coated graphite tube, of which the injection hole was enlarged to a diameter of approximately 5 mm. After introduction of the sample, 20 µl of 30 mg Pd/l in 1 mol/l HCl was added as a matrix modifier onto the hair sample. At the ashing stage of the furnace temperature program, air was passed through in the graphite tube at 600 ℃ for 1 min. By using the air ashing, the appearance times and shapes of the atomization signal of tin in the hair sample were similar to those for aqueous standard tin solution, indicating the possibility of direct calibration against aqueous standard solutions. The addition of Pd and HCl enhanced the absorbance of tin and improved the precision. Analytical results obtained for a hair sample and a hair reference material by the proposed method were in good agreement with those obtained by the conventional acid digestion method or reported values. (Received on August 9, 2001; Accepted on September 13, 2001) The contamination of the environment by tin compounds has became a serious problem. Tributyltin compounds have been used in antifouling paints for ships. Today, these organotin compounds are assumed endocrine disrupting chemicals whic
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