The Way We Live Now.

This is a personal account of one man's experience of the months during which COVID-19 spread in Australia. Though personal, it aims to also be representative, so that readers will find in it reflections of their own experiences. Various social incidents are described, some in which social distancing is involved. The altering states of the author's mind as time passes are carefully described in sequence, and the impact of continued anxiety and isolation on his mental well-being is presented as a form of madness, in one dramatic incident.

Effect of sleep quality on amnestic mild cognitive impairment vulnerable brain regions in cognitively normal elderly individuals.

STUDY OBJECTIVES: This study aims to evaluate the extent to which sleep quality impacts amnestic mild cognitive impairment (aMCI)-related brain regions in a cognitively normal cohort of individuals. METHODS: Seventy-four participants were rigorously evaluated using a battery of cognitive tests and a detailed clinical assessment to verify normal cognitive status. We then screened for sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and depressive symptoms using the Geriatric Depression Scale (GDS). Five subjects were excluded due to mild depression. Overall 38 individuals with mean age 70.7 ± 7 were classified as poor sleepers and 31 with mean age of 69.6 ± 6 years as normal sleepers. Structural MRI and Freesurfer brain parcellation were used to measure aMCI-related brain regions. RESULTS: Relative to normal sleepers, poor sleepers exhibited significant reductions in cortical and subcortical volumes bilaterally in the hippocampi, as well as in the superior parietal lobules and left amygdala. The effects were strongest in the left superior parietal lobule (p < .015), followed by the hippocampi. Diffuse patterns of cortical thinning were observed in the frontal lobes, but significant effects were concentrated in the right mesial frontal cortex. Lower sleep duration was most correlated with cortical volume and thickness reductions among all subjects. CONCLUSIONS: Atrophy related to poor sleep quality impacted a number of regions implicated in aMCI and Alzheimer's disease (AD). As such, interventions targeted towards improving sleep quality amongst the elderly may prove an effective tool for modulating the course of aMCI and AD.

Opposing functions of the ETS factor family define Shh spatial expression in limb buds and underlie polydactyly.

Sonic hedgehog (Shh) expression during limb development is crucial for specifying the identity and number of digits. The spatial pattern of Shh expression is restricted to a region called the zone of polarizing activity (ZPA), and this expression is controlled from a long distance by the cis-regulator ZRS. Here, members of two groups of ETS transcription factors are shown to act directly at the ZRS mediating a differential effect on Shh, defining its spatial expression pattern. Occupancy at multiple GABPα/ETS1 sites regulates the position of the ZPA boundary, whereas ETV4/ETV5 binding restricts expression outside the ZPA. The ETS gene family is therefore attributed with specifying the boundaries of the classical ZPA. Two point mutations within the ZRS change the profile of ETS binding and activate Shh expression at an ectopic site in the limb bud. These molecular changes define a pathogenetic mechanism that leads to preaxial polydactyly (PPD).

A wt1-controlled chromatin switching mechanism underpins tissue-specific wnt4 activation and repression.

Wt1 regulates the epithelial-mesenchymal transition (EMT) in the epicardium and the reverse process (MET) in kidney mesenchyme. The mechanisms underlying these reciprocal functions are unknown. Here, we show in both embryos and cultured cells that Wt1 regulates Wnt4 expression dichotomously. In kidney cells, Wt1 recruits Cbp and p300 as coactivators; in epicardial cells it enlists Basp1 as a corepressor. Surprisingly, in both tissues, Wt1 loss reciprocally switches the chromatin architecture of the entire Ctcf-bounded Wnt4 locus, but not the flanking regions; we term this mode of action "chromatin flip-flop." Ctcf and cohesin are dispensable for Wt1-mediated chromatin flip-flop but essential for maintaining the insulating boundaries. This work demonstrates that a developmental regulator coordinates chromatin boundaries with the transcriptional competence of the flanked region. These findings also have implications for hierarchical transcriptional regulation in development and disease.