Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process.

To understand the impact of epigenetics on human misfolding disease, we apply Gaussian-process regression (GPR) based machine learning (ML) (GPR-ML) through variation spatial profiling (VSP). VSP generates population-based matrices describing the spatial covariance (SCV) relationships that link genetic diversity to fitness of the individual in response to histone deacetylases inhibitors (HDACi). Niemann-Pick C1 (NPC1) is a Mendelian disorder caused by >300 variants in the NPC1 gene that disrupt cholesterol homeostasis leading to the rapid onset and progression of neurodegenerative disease. We determine the sequence-to-function-to-structure relationships of the NPC1 polypeptide fold required for membrane trafficking and generation of a tunnel that mediates cholesterol flux in late endosomal/lysosomal (LE/Ly) compartments. HDACi treatment reveals unanticipated epigenomic plasticity in SCV relationships that restore NPC1 functionality. GPR-ML based matrices capture the epigenetic processes impacting information flow through central dogma, providing a framework for quantifying the effect of the environment on the healthspan of the individual

Exercise interventions for maintaining cognitive function in cognitively healthy people in mid life

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effects ofexercise interventions on cognitive function in cognitively healthy people in mid life. We refer to Forbes 2015b for the review protocol on Exercise interventions for maintaining cognitive function in cognitively healthy people in late life and to Forbes 2015c for the review protocol on Exercise interventions for prevention of dementia in people with mild cognitive impairment

A gas-rich nuclear bar fuelling a powerful central starburst in NGC 2782

We present evidence that the peculiar interacting starburst galaxy NGC 2782 (Arp 215) harbors a gas-rich nuclear stellar bar feeding an M82-class powerful central starburst, from a study based on OVRO CO (J=1->0) data, WIYN BVR & Halpha observations, along with available NIR images, a 5 GHz RC map and HST images. NGC 2782 harbors a clumpy, bar-like CO feature of radius ~ 7.5'' (1.3 kpc) which leads a nuclear stellar bar of similar size. The nuclear CO bar is massive: it contains ~2.5x10**9 M_sun of molecular gas, which makes up ~ 8 % of the dynamical'mass present within a 1.3 kpc radius. Within the CO bar, emission peaks in two extended clumpy lobes which lie on opposite sides of the nucleus, separated by ~ 6'' (1 kpc). Between the CO lobes, in the inner 200 pc radius, resides a powerful central starburst which is forming stars at a rate of 3 to 6 M_sun yr-1. While circular motions dominate the CO velocity field, the CO lobes show weak bar-like streaming motions on the leading side of the nuclear stellar bar, suggestive of gas inflow. We estimate semi-analytically the gravitational torque from the nuclear stellar bar on the gas, and suggest large gas inflow rates from the CO lobes into the central starburst. These observations, which are amongst the first ones showing a nuclear stellar bar fuelling molecular gas into an intense central starburst, are consistent with simulations and theory which suggest that nuclear bars provide an efficient way of transporting gas closer to the galactic center to fuel central activity. Furthermore, several massive clumps are present at low radii, and dynamical friction might produce further gas inflow. We suggest that the nuclear molecular gas bas and central activity will be very short-lived, likely disappearing within 5x10**8 years.Comment: Accepted by the Astrophysical Journal, 10 pages, Latex with emulateapj.sty, apjfonts.sty, 10 postscript & 2 gif figure