Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian rhythm variant; affected individuals are “morning larks” with a 4-hour advance of the sleep, temperature, and melatonin rhythms. Here we report localization of the FASPS gene near the telomere of chromosome 2q. A strong candidate gene (h Per2 ), a human homolog of the period gene in Drosophila , maps to the same locus. Affected individuals have a serine to glycine mutation within the casein kinase I ɛ (CKI ɛ ) binding region of hPER2, which causes hypophosphorylation by CKI ɛ in vitro. Thus, a variant in human sleep behavior can be attributed to a missense mutation in a clock component, hPER2, which alters the circadian period.

Summary SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2 1 , and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro , the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.

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Familial advanced sleep phase syndrome (FASPS) is a human behavioural phenotype characterized by early sleep times and early-morning awakening. It was the first human, mendelian circadian rhythm variant to be well-characterized, and was shown to result from a mutation in a phosphorylation site within the casein kinase I (CKI)-binding domain of the human PER2 gene. To gain a deeper understanding of the mechanisms of circadian rhythm regulation in humans, we set out to identify mutations in human subjects leading to FASPS. We report here the identification of a missense mutation (T44A) in the human CKIdelta gene, which results in FASPS. This mutant kinase has decreased enzymatic activity in vitro. Transgenic Drosophila carrying the human CKIdelta-T44A gene showed a phenotype with lengthened circadian period. In contrast, transgenic mice carrying the same mutation have a shorter circadian period, a phenotype mimicking human FASPS. These results show that CKIdelta is a central component in the mammalian clock, and suggest that mammalian and fly clocks might have different regulatory mechanisms despite the highly conserved nature of their individual components.

This meta-analysis was conducted to understand the factors underlying effective messages to counter attitudes/beliefs based on misinformation. Because misinformation can lead to poor decisions about consequential matters and is persistent and difficult to correct, debunking it is an important scientific and public policy goal. This meta-analysis (k = 52, N = 6,878) revealed large effects for: presenting misinformation (2.41 ≤ d ≤ 3.08), debunking (1.14 ≤ d ≤ 1.33), and the persistence of misinformation in the face of debunking (0.75 ≤ d ≤ 1.06). Persistence was stronger and the debunking effect was weaker when audiences generated reasons in support of the initial misinformation. A detailed debunking message containing new details of the information currently recommended in various editorial policies, such as Retraction Watch, correlated positively with the debunking effect. Surprisingly, however, a detailed debunking message correlated positively with the misinformation-persistence effect. (141 words)