Runaway and walkaway stars from the ONC with Gaia DR2

Theory predicts that we should find fast, ejected (runaway) stars of all masses around dense, young star-forming regions. N-body simulations show that the number and distribution of these ejected stars could be used to constrain the initial spatial and kinematic substructure of the regions. We search for runaway and slower walkaway stars within 100 pc of the Orion Nebula Cluster (ONC) using Gaia DR2 astrometry and photometry. We compare our findings to predictions for the number and velocity distributions of runaway stars from simulations that we run for 4 Myr with initial conditions tailored to the ONC. In Gaia DR2, we find 31 runaway and 54 walkaway candidates based on proper motion, but not all of these are viable candidates in three dimensions. About 40 per cent are missing radial velocities, but we can trace back 9 3D-runaways and 24 3D-walkaways to the ONC, all of which are low/intermediate-mass (<8 M⊙). Our simulations show that the number of runaways within 100 pc decreases the older a region is (as they quickly travel beyond this boundary), whereas the number of walkaways increases up to 3 Myr. We find fewer walkaways in Gaia DR2 than the maximum suggested from our simulations, which may be due to observational incompleteness. However, the number of Gaia DR2 runaways agrees with the number from our simulations during an age of ∼1.3-2.4 Myr, allowing us to confirm existing age estimates for the ONC (and potentially other star-forming regions) using runaway stars

Epigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters

Growing evidence supports a role for deficient Wnt signalling in Alzheimer’s disease (AD). First, the Wnt antagonist DKK1 is elevated in AD brains and is required for amyloid-β-induced synapse loss. Second, LRP6 Wnt co-receptor is required for synapse integrity and three variants of this receptor are linked to late-onset AD. However, the expression/role of other Wnt signalling components remain poorly explored in AD. Wnt receptors Frizzled1 (Fzd1), Fzd5, Fzd7 and Fzd9 are of interest due to their role in synapse formation/plasticity. Our analyses showed reduced FZD1 and FZD7 mRNA levels in the hippocampus of human early AD stages and in the hAPPNLGF/NLGF mouse model. This transcriptional downregulation was accompanied by reduced levels of the pro-transcriptional histone mark H4K16ac and a concomitant increase of its deacetylase Sirt2 at Fzd1 and Fzd7 promoters in AD. In vitro and in vivo inhibition of Sirt2 rescued Fzd1 and Fzd7 mRNA expression and H4K16ac levels at their promoters. In addition, we showed that Sirt2 recruitment to Fzd1 and Fzd7 promoters is dependent on FoxO1 activity in AD, thus acting as a co-repressor. Finally, we found reduced levels of SIRT2 inhibitory phosphorylation in nuclear samples from human early AD stages with a concomitant increase in the SIRT2 phosphatase PP2C. This results in hyperactive nuclear Sirt2 and favours Fzd1 and Fzd7 repression in AD. Collectively, our findings define a novel role for nuclear hyperactivated SIRT2 in repressing Fzd1 and Fzd7 expression via H4K16ac deacetylation in AD. We propose SIRT2 as an attractive target to ameliorate AD pathology

Feature similarity gradients detect alterations in the neonatal cortex associated with preterm birth

The early life environment programmes cortical architecture and cognition across the life course. A measure of cortical organisation that integrates information from multi-modal MRI and is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover the perinatal origins of cortical health. Here, we use the Vogt-Bailey index to provide a fine-grained description of regional homogeneities and sharp variations in cortical microstructure based on feature gradients, and we investigate the impact of being born preterm on cortical development at term-equivalent age. Compared to term-born controls, preterm infants have a homogeneous microstructure in temporal and occipital lobes, and the medial parietal, cingulate, and frontal cortices, compared with term infants. These observations replicated across two independent datasets and were robust to differences that remain in the data after matching samples and alignment of processing and quality control strategies. We conclude that cortical microstructural architecture is altered in preterm infants in a spatially distributed rather than localised fashion.Keywords: feature similarity gradients, neonatal brain, preterm birth, MRI, neonatal corte