An amendment to this paper has been published and can be accessed via a link at the top of the paper.SARS-CoV-2 is the causative agent of the COVID-19 pandemic, with 10 million infections and more than 500,000 fatalities by June 2020. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface and fusion of the viral and host membranes. Prefusion SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design. However, its limited stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a construct corresponding to the prefusion SARS-CoV-2 S ectodomain trimer, covalently stabilized by a disulfide bond in the closed conformation. Structural and antigenicity analyses show we successfully shut S in the closed state without otherwise altering its architecture. We demonstrate that this strategy is applicable to other β-coronaviruses, such as SARS-CoV and MERS-CoV, and might become an important tool for structural biology, serology, vaccine design and immunology studies.Despite the clinical usefulness of self-measured home blood pressure (BP), reports on the characteristics of home BP have not been sufficient and have varied due to the measurement conditions in each study. We constructed a database on self-measured home BP, which included five Japanese general populations as subdivided aggregate data that were clustered and meta-analyzed according to sex, age category, and antihypertensive drug treatment at baseline (treated and untreated). The self-measured home BPs were collected after a few minutes of rest in a sitting position (1) the morning home BP was measured within 1 h of waking, after urination, before breakfast, and before taking antihypertensive medication (if any); and (2) the evening home BP was measured just before going to bed. The pulse rate was simultaneously measured. Eligible data from 2000 onward were obtained. The morning BP was significantly higher in treated participants than in untreated people of the same age category, and the BP difference was more marked in women. Among untreated residents, home systolic/diastolic BPs measured in the morning were higher than those measured in the evening; the differences were 5.7/5.0 mmHg in women (ranges across the cohorts, 5.3-6.8/4.7-5.4 mmHg) and 7.3/7.7 mmHg in men (ranges, 6.4-8.5/7.0-8.7 mmHg). In contrast, the home pulse rate in women and men was 2.4 (range, 1.5-3.7) and 5.6 (range, 4.6-6.6) beats per minute, respectively, higher in the evening than in the morning. We demonstrated the current status of home BP and home pulse rate in relation to sex, age, and antihypertensive treatment status in the Japanese general population. The approach by which fine-clustered aggregate statistics were collected and integrated could address practical issues raised in epidemiological research settings.Coronary artery calcification (CAC), a marker of atherosclerosis, is predictive of incident hypertension based on the 2017 ACC/AHA high blood pressure guidelines. We performed a large cohort study to investigate whether incident hypertension could be predicted from CAC measurements as a measure of atherosclerosis, even when updated hypertension criteria are applied. A total of 27,918 male subjects who underwent CAC examination during a health screening program between 2011 and 2017 were enrolled. According to the 2017 ACC/AHA guidelines, hypertension was defined as 130/80 mmHg. Cox proportional hazard analysis was used to assess the risk of incident hypertension according to CAC categories (CAC = 0, 1-10, 11-100, >100). After exclusion, 14,335 subjects were included (mean age 40.0 [5.7] years). During the follow-up period (median 3.63 years), 3050 subjects (21.3%) developed hypertension. The subjects in the highest CAC category showed an increased risk of hypertension compared with the lowest CAC category, as confirmed by multivariate adjusted hazard ratios of 1.27 (95% confidence interval [CI], 1.01-1.60; P  less then  0.001). The increased risk of developing hypertension was consistent after adjustments were made for several confounding factors. The CAC score, a marker of atherosclerosis, is positively associated with incident hypertension according to the updated 2017 ACC/AHA guidelines.Genetic isolation due to geographic separation (vicariance) is the best understood cause of vertebrate speciation. Nevertheless, it has never been demonstrated in the fossil record across a wide range of taxa. Selleck Pexidartinib Here, by reviewing in-depth the available data of the Late Palaeozoic (~ 350-250 million years ago), I reconstructed an early Pangaean junction-disjunction palaeogeographic model and showed that it coincides strongly with time-calibrated cladograms of the Late Palaeozoic synapsids (the primitive ancestors of modern mammals). The temporal development of the vicariant topology seems to fit closely with the emergence rhythm of the recovered synapsid taxa, suggesting vicariance due to Pangaean separation as the cause of early amniote evolution. The inferred vicariant topology also accounts for the observed pattern in the North American marine biostratigraphic units. Accordingly, the model demonstrates the link between the evolution of life on Earth and palaeogeographic evolution and strongly supports allopatric speciation through vicariance as the prominent mode of amniote evolution. Furthermore, correlations between state-of-the-art biochronostratigraphic charts and this palaeogeographic model suggest that the arido-eustasy model can explain the mid-Permian biotic extinction event and depositional cycles, such as the pre-Zechstein of the Central European Basin.The thermal tolerances of vertebrates are generally restricted to body temperatures below 45-47 °C, and avian and mammalian critical thermal maxima seldom exceed 46 °C. We investigated thermoregulation at high air temperatures in the red-billed quelea (Quelea quelea), an African passerine bird that occurs in flocks sometimes numbering millions of individuals. Our data reveal this species can increase its body temperature to extremely high levels queleas exposed to air temperature > 45 °C increased body temperature to 48.0 ± 0.7 °C without any apparent ill-effect, with individual values as high as 49.1 °C. These values exceed known avian lethal limits, with tolerance of body temperature > 48 °C unprecedented among birds and mammals.