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

Mother–calf interactions and social behavior development in Commerson’s dolphins (Cephalorhynchus commersonii)

Mother–calf interactions and the behaviors of mothers during separation from their calves were examined in four Commerson’s dolphin (Cephalorhynchus commersonii) mother–calf pairs. Four infants were observed: 56.8 h over 30 days from birth to 263 days of age, 36.9 h over 20 days from birth to 149 days of age, 10.4 h over 3 days from birth to 2 days of age, and 15.0 h over 3 days from birth to 2 days of age. All four pairs shared common characteristics in the rate and frequencies of mother–calf interactions and the behaviors of mothers during the first week of life. After the first week, individual differences in changes in the frequency of each behavior were observed. The three behaviors considered representative of maternal care (parallel swimming, synchronous breathing, and body-to-body contact) were frequently performed in the first week; thereafter, the frequencies declined. Separate behaviors of mothers were infrequent during the first week and increased with an increase in infants’ age. Bumping by infants increased with time, suggesting an increase in soliciting by calves and conflict between mothers and calves. The frequency of flipper-to-body rubbing also changed but in a complex manner, probably because the calves needed to learn how to perform this behavior from their mothers and because initiator and recipient of this behavior can be changed quickly

Sound variation and function in captive Commerson's dolphins (Cephalorhynchus commersonii)

Commerson's dolphin (Cephalorhynchus commersonii), one of the smallest dolphin species, has been reported to produce only narrow-band high-frequency (NBHF) clicks and no whistles. To clarify their sound repertoire and examine the function of each type, we analysed the sounds and behaviour of captive Commerson's dolphins in Toba Aquarium, Japan. All recorded sounds were NBHF clicks with peak frequency >110 kHz. The recorded click-trains were categorised into four types based on the changing pattern of their Inter-click intervals (ICI): Decreasing type, with continuously decreasing ICI during the last part of the train; Increasing type, with continuously increasing ICI during the last part; Fluctuating type, with fluctuating ICI; and Burst-pulse type, with very short and constant ICI. The frequency of the Decreasing type increased when approaching an object newly introduced to the tank, suggesting that the sound is used for echolocation on approach. The Burst-pulse type suddenly increased in front of the object and was often oriented towards it, suggesting that it was used for echolocation in close proximity to the object. In contrast, the Increasing type was rarely recorded during approach, but increased when a dolphin approached another dolphin. The Increasing and Burst-pulse types also increased when dolphins began social behaviours. These results suggest that some NBHF clicks have functions other than echolocation, such as communication

Development of a picture-scale-questionnaire to assess liking for fatty, salty, sweet, and umami seasonings compared to a sensory evaluation for Japanese consumers

International audiencePrefQuest is a web-based questionnaire that measures the liking for sweet, fatty-sweet, salty, and fatty-salty sensations using combinations of images of French food items. We adapted the original PrefQuest questionnaire for Japanese respondents (J-PrefQuest). J-PrefQuest comprises 17 Japanese food items categorized into four sensations: fatty, salty, sweet, and umami. Participants responded by indicating their preferred level of seasoning for each food item on a 6-point scale. Segmentation of 161 respondents identified groups who preferred: (a) high amount of umami seasonings; (b) low amount of umami seasonings; (c) high amount of fatty and low amount of salty seasonings. To validate the questionnaire, 70 female university students were recruited for a sensory evaluation of five levels of seasoning used for six food items on a 9-point hedonic scale before completing the questionnaire. The validity of J-PrefQuest questionnaire was then analyzed by comparing the two results. Practical applicationsMeasuring personal preference or liking for the taste of food items is important as such information may contribute to the prevention of various diseases and improve the quality of life of consumers. We developed a simple questionnaire with pictures to evaluate the liking for fatty, salty, sweet, and umami sensations of Japanese respondents. This questionnaire focuses on typical seasonings added to different Japanese food items and provides objective information about liking different food sensations. Thus, it has application as an important screening tool to identify respondents who may need to make their food consumption behavior more healthy. Moreover, following minor modifications, this questionnaire could also be used in other Asian countries where plain white rice is the stable food

Mycobacterium ulcerans Infection in an Indian Flap-Shelled Turtle (Lissemys punctata punctata)

We report an atypical mycobacterial infection in an Indian flap-shelled turtle, Lissemys punctata punctata, that died in an aquarium in Japan. At necropsy, the turtle showed multiple white nodules on the capsular surface and parenchyma of various organs such as the liver, spleen, intestine, and lung. Histologically, granulomatous inflammation surrounding a central zone of necrosis was observed. Sections stained by the Ziehl-Neelsen method revealed numerous acid-fast bacilli in the cytoplasm of macrophages and in the central area of necrosis. The organisms were identified as a mycobacterial species by PCR and nucleotide sequence analysis and revealed 98-100% homology to M. ulcerans. This is, to our knowledge, the first report of mycobacteriosis due to M. ulcerans in a turtle