Alike but not the same: Psychological profiles of COVID-19 vaccine skeptics.

One of the challenges of the SARS-CoV-2 pandemic was a widespread skepticism about vaccination. To elucidate the underlying mental and emotional predispositions, we examined a sample of 1428 participants using latent profile analysis (LPA) on selected personality trait variables, mental health status, and measures of irrational beliefs. LPA revealed five distinct profiles: two classes of non-skeptics and three of skeptics. The smaller non-skeptic class reported the highest rates of mental health problems, along with high levels of neuroticism, hostility, interpersonal sensitivity, and external locus of control. The larger non-skeptic class was psychologically well-balanced. Conversely, the skeptic groups shared strong distrust of COVID-19 vaccination but differed in emotional and mental profiles, leading to graded differences in endorsing extreme conspiracy beliefs. This suggests that vaccine skepticism is not solely a result of mental illness or emotional instability; rather extreme skepticism manifests as a nuanced, graded phenomenon contingent on personality traits and conspirational beliefs.

En2, Pax2/5 and Tcf-4 transcription factors cooperate in patterning the Xenopus brain.

Among Xenopus Lef/Tcfs, XTcf-4 has an outstanding role. In early development it is located exclusively in the midbrain where it is essential for midbrain and isthmus development. In order to identify transcription factors responsible for the restriction of XTcf-4 expression we isolated a 3.8kb fragment of the XTcf-4 promoter. We found that this promoter fragment is sufficient to mimic endogenous XTcf-4 expression in the midbrain. Characterization of putative binding sites for en2 and pax2/5 revealed that en2, but not pax2/5 directly represses XTcf-4 promoter activity. Gain-of-function experiments in Xenopus embryos confirmed this en2-mediated repression. Loss-of-function experiments demonstrate that both en2 and pax2/5 are essential for endogenous XTcf-4 expression. The primary effect of pax2/5 depletion thereby appears to be a reduced en2 expression at neurula stages. Because en2 can compensate for the depletion of pax2/5, we assume a hierarchical regulation of gene expression in the midbrain/isthmus region with pax2/5 acting upstream of en2. Furthermore, since the XTcf-4 expression domain does not overlap with the expression domains of the isthmus marker genes en2 and pax2/5, we conclude that the knock-down of en2 and pax2/5 results in a downregulation of a paracrine growth factor regulating XTcf-4 expression. We found that the growth factor for this non-cell-autonomous effect of en2 and pax2/5 is wnt-1 acting on the -1437 Lef/Tcf binding site on the XTcf-4 promoter. We provide evidence that the main nuclear wnt transducer for the autoregulation of XTcf-4 is XTcf-1.