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

PRELIMINARY ANALYSIS OF TEMPERATURE CHANGES DUE TO SYNOPTIC SCALE DISTURBANCES AT SYOWA STATION, ANTARCTICA IN WINTER

The Antarctic surface air temperature often increases severely in winter when a synoptic scale disturbance comes close and then decreases after it goes away. The mechanism of these temperature changes in analyzed from the data observed at Syowa Station, Antarctica in 1993 by the 34th Japanese Antarctic Research Expedition (JARE-34). For this purpose, fifteen cases each are selected for both the prominent warming and the succeeding cooling events in winter. The magnitude of changes in temperature due to destruction or reformation of the surface temperature inversion during the events is estimated from comparison of the vertical temperature profiles above Syowa Station before and after each events. Its contribution amounts to about half of the observed change in the surface temperature.The horizontal advection of sensible heat is calculated from the thermal wind shear relation. It is shown that the horizontal advection of warm and cold air are observed in the warming and the cooling events, respectively. It is estimated from the average heat budget that there should be an upward current of 0.2 to 0.8 (cms)^ during the warming events and a downward current of less than 0.4 (cms)^ during the cooling events in the 850 to 300 hPa layer

Thermal structure of proglacial lakes in Patagonia

Calving glaciers are rapidly retreating in many regions under the influence of ice-water interactions at the glacier front. In contrast to the numerous researches conducted on fjords in front of tidewater glaciers, very few studies have been reported on lakes in which freshwater calving glaciers terminate. To better understand ice-water interactions at the front of freshwater calving glaciers, we measured lakewater temperature, turbidity, and bathymetry near Glaciar Perito Moreno, Upsala, and Viedma, large calving glaciers of the Southern Patagonia Icefield. The thermal structures of these lakes were significantly different from those reported in glacial fjords. There was no indication of upwelling subglacial meltwater; instead, turbid and cold glacial water discharge filled the region near the lake bottom. This was because water density was controlled by suspended sediment concentrations rather than by water temperature. Near-surface wind-driven circulation reaches a depth of similar to 180 m, forming a relatively warm isothermal layer (mean temperature of similar to 5-6 degrees C at Perito Moreno, similar to 3-4 degrees C at Upsala, and similar to 6-7 degrees C at Viedma), which should convey heat energy to the ice-water interface. However, the deeper part of the glacier front is in contact with stratified cold water, implying a limited amount of melting there. In the lake in front of Glaciar Viedma, the region deeper than 120 m was filled entirely with turbid and very cold water at pressure melting temperature. Our results revealed a previously unexplored thermal structure of proglacial lakes in Patagonia, suggesting its importance in the subaqueous melting of freshwater calving glaciers

Experimental Study on Evaporation Characteristics of Light Cycle Oil Droplet under Various Ambient Conditions

The authors conducted droplet evaporation experiments of light cycle oil (LCO) at various ambient temperatures and pressures. Five kinds of LCO and three kinds of arranged fuels were used. We investigated the evaporation characteristics of LCO and the relationships between the evaporation characteristics and the cetane index. In addition to that, a surrogate fuel composed of four chemical species, which can simulate the droplet evaporation characteristics of LCO, was suggested. Experimental results show that the differences in droplet lifetime between fuel species become larger with decreasing ambient temperature. This is because the low volatile component made the evaporation rate outstandingly slow at a low ambient temperature. It was found that the relationship between droplet lifetime and the late-stage distillation temperature becomes stronger at low ambient temperature and high ambient pressure. By an analysis employing the properties of chemical species in LCO surrogate fuel, it is clarified that the mass evaporation rate becomes smaller than the internal diffusion, which is the condition similar to that in the distillation test. Finally, the relationship between the droplet lifetime and the cetane index was investigated. It can be concluded that the droplet lifetime is independent of the cetane index under all conditions tested in this study. The experimental data obtained by this research can be utilized for the validation of multicomponent fuel droplet evaporation models in the future

南パタゴニア氷原ペリート・モレノ氷河における熱水掘削

Glaciar Perito Moreno is one of the major freshwater calving glaciers in the Southern Patagonia Icefield. Its fast-flowing characteristic is probably due to high water pressure at the glacier bed, however, subglacial conditions have never been observed in Patagonia until our recent undertaking. To investigate the role of subglacial water pressure in the calving glacier dynamics, we performed hot-water drilling at Glaciar Perito Moreno from February to March 2010. This study represents the first attempt ever at hot-water glacier drilling in Patagonia. Two boreholes were drilled to the bed at 4.7km upglacier from the terminus, where the ice was revealed to be 515±5m thick and the bed located at about 330m below the proglacial lake level. The water levels in the boreholes were >100m above the lake level, which indicates that more than 90% of the ice overburden pressure was balanced out by the subglacial water pressure. Water in the boreholes had drained away before the drilling reached the bed, suggesting the existence of an englacial drainage system. These results provide crucial information for understanding the hydraulic and hydrological conditions of calving glaciers. In order to drill a 500m deep glacier, an existing hot-water drilling system was adapted by increasing the number of high-pressure hot-water machines. The drilling operation at Glaciar Perito Moreno confirmed the system's capacity to drill a 500-m-deep borehole at a rate of 50mh-1 with fuel consumption rates of 15.7lh-1 for diesel and 3.9lh-1 for petrol