Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease caused by motor neuron loss, resulting in muscle wasting, paralysis and eventual death. A key pathological feature of ALS is cytoplasmically mislocalized and aggregated TDP-43 protein in >95% of cases, which is considered to have prion-like properties. Historical studies have predominantly focused on genetic forms of ALS, which represent ∼10% of cases, leaving the remaining 90% of sporadic ALS relatively understudied. Additionally, the role of astrocytes in ALS and their relationship with TDP-43 pathology is also not currently well understood. We have therefore used highly enriched human induced pluripotent stem cell (iPSC)-derived motor neurons and astrocytes to model early cell type-specific features of sporadic ALS. We first demonstrate seeded aggregation of TDP-43 by exposing human iPSC-derived motor neurons to serially passaged sporadic ALS post-mortem tissue (spALS) extracts. Next, we show that human iPSC-derived motor neurons are more vulnerable to TDP-43 aggregation and toxicity compared with their astrocyte counterparts. We demonstrate that these TDP-43 aggregates can more readily propagate from motor neurons into astrocytes in co-culture paradigms. We next found that astrocytes are neuroprotective to seeded aggregation within motor neurons by reducing (mislocalized) cytoplasmic TDP-43, TDP-43 aggregation and cell toxicity. Furthermore, we detected TDP-43 oligomers in these spALS spinal cord extracts, and as such demonstrated that highly purified recombinant TDP-43 oligomers can reproduce this observed cell-type specific toxicity, providing further support to a protein oligomer-mediated toxicity hypothesis in ALS. In summary, we have developed a human, clinically relevant, and cell-type specific modelling platform that recapitulates key aspects of sporadic ALS and uncovers both an initial neuroprotective role for astrocytes and the cell type-specific toxic effect of TDP-43 oligomers

Secularly powered outflows from AGN:the dominance of non-merger driven supermassive black hole growth

Recent observations and simulations have revealed the dominance of secular processes over mergers in driving the growth of both supermassive black holes (SMBH) and galaxy evolution. Here we obtain narrowband imaging of AGN powered outflows in a sample of 12 galaxies with disk-dominated morphologies, whose history is assumed to be merger-free. We detect outflows in 10/12 sources in narrow band imaging of the [ O III] 5007Å emission using filters on the Shane-3m telescope. We calculate a mean outflow rate for these AGN of 0.95± 0.14 {M}_{☉ } {yr}^{-1}. This exceeds the mean accretion rate of their SMBHs (0.054± 0.039 {M}_{☉ } {yr}^{-1}) by a factor of ̃18. Assuming that the galaxy must provide at least enough material to power both the AGN and the outflow, this gives a lower limit on the average inflow rate of ̃ 1.01± 0.14 {M}_{☉ } {yr}^{-1}, a rate which simulations show can be achieved by bars, spiral arms and cold accretion. We compare our disk dominated sample to a sample of nearby AGN with merger dominated histories and show that the black hole accretion rates in our sample are 5 times higher (4.2σ) and the outflow rates are 5 times lower ( 2.6σ). We suggest that this could be a result of the geometry of the smooth, planar inflow in a secular dominated system, which is both spinning up the black hole to increase accretion efficiency and less affected by feedback from the outflow, than in a merger-driven system with chaotic quasi-spherical inflows. This work provides further evidence that secular processes are sufficient to fuel SMBH growth...

Evidence for non-merger co-evolution of galaxies and their supermassive black holes

Recent observational and theoretical studies have suggested that supermassive black holes (SMBHs) grow mostly through non-merger (`secular') processes. Since galaxy mergers lead to dynamical bulge growth, the only way to observationally isolate non-merger growth is to study galaxies with low bulge-to-total mass ratio (e.g. B/T < 10%). However, bulge growth can also occur due to secular processes, such as disk instabilities, making disk-dominated selections a somewhat incomplete way to select merger-free systems. Here we use the Horizon-AGN simulation to select simulated galaxies which have not undergone a merger since z = 2, regardless of bulge mass, and investigate their location on typical black hole-galaxy scaling relations in comparison to galaxies with merger dominated histories. While the existence of these correlations has long been interpreted as co-evolution of galaxies and their SMBHs driven by galaxy mergers, we show here that they persist even in the absence of mergers. We find that the correlations between SMBH mass and both total mass and stellar velocity dispersion are independent of B/T ratio for both merger-free and merger-dominated galaxies. In addition, the bulge mass and SMBH mass correlation is still apparent for merger-free galaxies, the intercept for which is dependent on B/T. Galaxy mergers reduce the scatter around the scaling relations, with merger-free systems showing broader scatter. We show that for merger-free galaxies, the co-evolution is dominated by radio-mode feedback, and suggest that the long periods of time between galaxy mergers make an important contribution to the co-evolution between galaxies and SMBHs in all galaxies.Comment: RJS and RSB are joint first authors. 12 pages, 7 figures, submitted to MNRA

Supermassive black holes in merger-free galaxies have higher spins which are preferentially aligned with their host galaxy

Here we use the Horizon-AGN simulation to test whether the spins of SMBHs in merger-free galaxies are higher. We select samples using an observationally motivated bulge-to-total mass ratio of < 0.1, along with two simulation motivated thresholds selecting galaxies which have not undergone a galaxy merger since z = 2, and those SMBHs with < 10% of their mass due to SMBH mergers. We find higher spins (> 5{\sigma} ) in all three samples compared to the rest of the population. In addition, we find that SMBHs with their growth dominated by BH mergers following galaxy mergers, are less likely to be aligned with their galaxy spin than those that have grown through accretion in the absence of galaxy mergers (3.4{\sigma} ). We discuss the implications this has for the impact of active galactic nuclei (AGN) feedback, finding that merger-free SMBHs spend on average 91% of their lifetimes since z = 2 in a radio mode of feedback (88% for merger-dominated galaxies). Given that previous observational and theoretical works have concluded that merger-free processes dominate SMBH-galaxy co-evolution, our results suggest that this co-evolution could be regulated by radio mode AGN feedback.Comment: RSB and RJS are joint first authors. Submitted to MNRAS, 10 page

Galaxy Zoo: evidence for diverse star formation histories through the green valley

Does galaxy evolution proceed through the green valley via multiple pathways or as a single population? Motivated by recent results highlighting radically different evolutionary pathways between early- and late-type galaxies, we present results from a simple Bayesian approach to this problem wherein we model the star formation history (SFH) of a galaxy with two parameters, [t, τ] and compare the predicted and observed optical and near-ultraviolet colours. We use a novel method to investigate the morphological differences between the most probable SFHs for both disc-like and smooth-like populations of galaxies, by using a sample of 126 316 galaxies (0.01 < z < 0.25) with probabilistic estimates of morphology from Galaxy Zoo. We find a clear difference between the quenching time-scales preferred by smooth- and disc-like galaxies, with three possible routes through the green valley dominated by smooth- (rapid time-scales, attributed to major mergers), intermediate- (intermediate time-scales, attributed to minor mergers and galaxy interactions) and disc-like (slow time-scales, attributed to secular evolution) galaxies. We hypothesize that morphological changes occur in systems which have undergone quenching with an exponential time-scale τ < 1.5 Gyr, in order for the evolution of galaxies in the green valley to match the ratio of smooth to disc galaxies observed in the red sequence. These rapid time-scales are instrumental in the formation of the red sequence at earlier times; however, we find that galaxies currently passing through the green valley typically do so at intermediate time-scales.