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

Iron speciation and mineral characterization of contaminated sediments by coal mining drainage in Neath Canal, South Wales, United Kingdom

In the early 1990’s, the Neath Canal in South Wales, UK, received large amounts of drainage waters from nearby coal mines, which contributed to its contamination by heavy metals and arsenic. One sediment core and surface sediments were collected from the upstream section of the Neath Canal and characterized for their mineral composition and iron speciation using powder X-ray diffraction (XRD) and Mössbauer spectroscopy. The sediments show three distinctive layers that are defined by their physical properties including color, sediment components and dryness. The upper layer of the sediment (0–22 cm) is a reddish-brown wet precipitate dominated by iron oxides and hydroxides and a high content of arsenic. The middle layer (22–27 cm) is a soft wet deposit of yellow color which mainly contains calcite with sheet silicates (kaolinite) and goethite. Magnesium, calcium and manganese are enriched in this layer whereas iron is depleted compared to the upper layer. The lower part of the core (below 27 cm) is colored gray to dark gray and contains quartz, pyrite and clay minerals, similar to normal aquatic sediments. In addition, this layer also contains abundant coal particles. Silicon, aluminium, titanium, potassium, phosphorus and sodium concentrations are higher whereas iron, manganese, calcium and magnesium are lower in the lower portion of the core compared to the middle and upper layers. Mineral composition, major elements, and iron speciation indicate oxic conditions in the upper and middle layers whereas reducing conditions prevail in the lower layer, which likely control the distribution of hazardous elements. Given the variation of physico-chemical characteristics of the sediments with depth in the canal, different remediation treatments will likely be necessary for each layer of sediments

Landside tritium leakage over through years from Fukushima Dai‑ichi nuclear plant and relationship between countermeasures and contaminated water

There has been tritium groundwater leakage to the land side of Fukushima Dai-ichi nuclear power plants since 2013. Groundwater was continuously collected from the end of 2013 to 2019, with an average tritium concentration of approximately 20 Bq/L. Based on tritium data published by Tokyo Electric Power Company Holdings (TEPCO) (17,000 points), the postulated source of the leakage was (1) leaks from a contaminated water tank that occurred from 2013 to 2014, or (2) a leak of tritium that had spread widely over an impermeable layer under the site. Based on our results, sea side and land side tritium leakage monitoring systems should be strengthened