Modular reorganization of the global network of gene regulatory interactions during perinatal human brain development.

BACKGROUND During early development of the nervous system, gene expression patterns are known to vary widely depending on the specific developmental trajectories of different structures. Observable changes in gene expression profiles throughout development are determined by an underlying network of precise regulatory interactions between individual genes. Elucidating the organizing principles that shape this gene regulatory network is one of the central goals of developmental biology. Whether the developmental programme is the result of a dynamic driven by a fixed architecture of regulatory interactions, or alternatively, the result of waves of regulatory reorganization is not known. RESULTS Here we contrast these two alternative models by examining existing expression data derived from the developing human brain in prenatal and postnatal stages. We reveal a sharp change in gene expression profiles at birth across brain areas. This sharp division between foetal and postnatal profiles is not the result of pronounced changes in level of expression of existing gene networks. Instead we demonstrate that the perinatal transition is marked by the widespread regulatory rearrangement within and across existing gene clusters, leading to the emergence of new functional groups. This rearrangement is itself organized into discrete blocks of genes, each targeted by a distinct set of transcriptional regulators and associated to specific biological functions. CONCLUSIONS Our results provide evidence of an acute modular reorganization of the regulatory architecture of the brain transcriptome occurring at birth, reflecting the reassembly of new functional associations required for the normal transition from prenatal to postnatal brain development

Dynamic Chromatin Localization of Sirt6 Shapes Stress- and Aging-Related Transcriptional Networks

The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-κB and regulate some NF-κB target genes, but the full scope of Sirt6 target genes as well as dynamics of Sirt6 occupancy on chromatin are not known. Here we map Sirt6 occupancy on mouse promoters genome-wide and show that Sirt6 occupancy is highly dynamic in response to TNF-α. More than half of Sirt6 target genes are only revealed upon stress-signaling. The majority of genes bound by NF-κB subunit RelA recruit Sirt6, and dynamic Sirt6 relocalization is largely driven in a RelA-dependent manner. Integrative analysis with global gene expression patterns in wild-type, Sirt6−/−, and double Sirt6−/− RelA−/− cells reveals the epistatic relationships between Sirt6 and RelA in shaping diverse temporal patterns of gene expression. Genes under the direct joint control of Sirt6 and RelA include several with prominent roles in cell senescence and organismal aging. These data suggest dynamic chromatin relocalization of Sirt6 as a key output of NF-κB signaling in stress response and aging

OGLE-2017-BLG-1186: first application of asteroseismology and Gaussian processes to microlensing

We present the analysis of the event OGLE-2017-BLG-1186 from the 2017 Spitzer microlensing campaign. This is a remarkable microlensing event because its source is photometrically bright and variable, which makes it possible to perform an asteroseismic analysis using ground-based data. We find that the source star is an oscillating red giant with average timescale of ∼9 days. The asteroseismic analysis also provides us source properties including the source angular size (∼27μas) and distance (∼11.5 kpc), which are essential for inferring the properties of the lens. When fitting the light curve, we test the feasibility of Gaussian Processes (GPs) in handling the correlated noise caused by the variable source. We find that the parameters from the GP model are generally more loosely constrained than those from the traditional χ2 minimization method. We note that this event is the first microlensing system for which asteroseismology and GPs have been used to account for the variable source. With both finite-source effect and microlens parallax measured, we find that the lens is likely a ∼0.045 M⊙ brown dwarf at distance ∼9.0 kpc, or a ∼0.073 M⊙ ultracool dwarf at distance ∼9.8 kpc. Combining the estimated lens properties with a Bayesian analysis using a Galactic model, we find a 35% probability for the lens to be a bulge object and 65% to be a background disk object

VLT, GROND, AND DANISH TELESCOPE OBSERVATIONS OF TRANSITS IN THE TRAPPIST-I SYSTEM

TRAPPIST-1 is an ultra-cool dwarf that hosts seven known transiting planets. We present photometry of the system obtained using three telescopes at ESO La Silla (the Danish 1.54 m telescope and the 2.2 m MPI telescope) and Paranal (Unit Telescope 1 of the Very Large Telescope). We obtained 18 light curves from the Danish telescope, eight from the 2.2 m and four from the VLT. From these we measure 25 times of mid-transit for four of the planets (b, c, f, g). These light curves and times of mid-transit will be useful in determining the masses and radii of the planets, which show variations in their transit times due to gravitational interactions

OGLE-2017-BLG-1434Lb: Eighth <i>q</i><1×10⁻⁴ Mass-Ratio Microlens Planet Confirms Turnover in Planet Mass-Ratio Function

We report the discovery of a cold Super-Earth planet (mp=4.4±0.5 M⊕) orbiting a low-mass (M=0.23±0.03) M⊙ dwarf at projected separation a⊥=1.18±0.10 a.u., i.e., about 1.9 times the distance the snow line. The system is quite nearby for a microlensing planet, DL=0.86±0.09 kpc. Indeed, it was the large lens-source relative parallax πrel=1.0 mas (combined with the low mass M) that gave rise to the large, and thus well-measured, "microlens parallax" πE∝(πrel/M)1/2 that enabled these precise measurements. OGLE-2017-BLG-1434Lb is the eighth microlensing planet with planet-host mass ratio q-4. We apply a new planet-detection sensitivity method, which is a variant of "V/Vmax", to seven of these eight planets to derive the mass-ratio function in this regime. We find dN/d lnq ∝ qp, with p=1.05+0.78-0.68, which confirms the "turnover" in the mass function found by Suzuki et al. relative to the power law of opposite sign n=-0.93±0.13 at higher mass ratios q≳2×10-4. We combine our result with that of Suzuki et al. to obtain p=0.73+0.42-0.34