4 research outputs found
The balance of power: accretion and feedback in stellar mass black holes
In this review we discuss the population of stellar-mass black holes in our
galaxy and beyond, which are the extreme endpoints of massive star evolution.
In particular we focus on how we can attempt to balance the available accretion
energy with feedback to the environment via radiation, jets and winds,
considering also possible contributions to the energy balance from black hole
spin and advection. We review quantitatively the methods which are used to
estimate these quantities, regardless of the details of the astrophysics close
to the black hole. Once these methods have been outlined, we work through an
outburst of a black hole X-ray binary system, estimating the flow of mass and
energy through the different accretion rates and states. While we focus on
feedback from stellar mass black holes in X-ray binary systems, we also
consider the applicability of what we have learned to supermassive black holes
in active galactic nuclei. As an important control sample we also review the
coupling between accretion and feedback in neutron stars, and show that it is
very similar to that observed in black holes, which strongly constrains how
much of the astrophysics of feedback can be unique to black holes.Comment: To be published in Haardt et al. Astrophysical Black Holes. Lecture
Notes in Physics. Springer 201
CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice
Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases
Orexin-A activates locus coeruleus cell firing and increases arousal in the rat
Original article can be found at: http://www.pnas.org/ Copyright by The National Academy of Sciences [Full text of this article is not available in the UHRA]Peer reviewe