Stars made in outflows may populate the stellar halo of the Milky Way

We study stellar-halo formation using six Milky-Way-mass galaxies in FIRE-2 cosmological zoom simulations. We find that 5-40 per cent of the outer (50-300 kpc) stellar halo in each system consists of in-situ stars that were born in outflows from the main galaxy. Outflow stars originate from gas accelerated by superbubble winds, which can be compressed, cool, and form co-moving stars. The majority of these stars remain bound to the halo and fall back with orbital properties similar to the rest of the stellar halo at z = 0. In the outer halo, outflow stars are more spatially homogeneous, metal-rich, and alpha-element-enhanced than the accreted stellar halo. At the solar location, up to ∼10 per cent of our kinematically identified halo stars were born in outflows; the fraction rises to as high as ∼40 per cent for the most metal-rich local halo stars ([Fe/H] >-0.5). Such stars can be retrograde and create features similar to the recently discoveredMilkyWay 'Splash' in phase space.We conclude that theMilkyWay stellar halo could contain local counterparts to stars that are observed to form in molecular outflows in distant galaxies. Searches for such a population may provide a new, near-field approach to constraining feedback and outflow physics. A stellar halo contribution from outflows is a phase-reversal of the classic halo formation scenario of Eggen, Lynden-Bell & Sandange, who suggested that halo stars formed in rapidly infalling gas clouds. Stellar outflows may be observable in direct imaging of external galaxies and could provide a source for metal-rich, extreme-velocity stars in the Milky Way

A Relationship Between Stellar Metallicity Gradients and Galaxy Age in Dwarf Galaxies

We explore the origin of stellar metallicity gradients in simulated and observed dwarf galaxies. We use FIRE-2 cosmological baryonic zoom-in simulations of 26 isolated galaxies as well as existing observational data for 10 Local Group dwarf galaxies. Our simulated galaxies have stellar masses between $10^{5.5}$ and 10^{8.6} \msun. Whilst gas-phase metallicty gradients are generally weak in our simulated galaxies, we find that stellar metallicity gradients are common, with central regions tending to be more metal-rich than the outer parts. The strength of the gradient is correlated with galaxy-wide median stellar age, such that galaxies with younger stellar populations have flatter gradients. Stellar metallicty gradients are set by two competing processes: (1) the steady "puffing" of old, metal-poor stars by feedback-driven potential fluctuations, and (2) the accretion of extended, metal-rich gas at late times, which fuels late-time metal-rich star formation. If recent star formation dominates, then extended, metal-rich star formation washes out pre-existing gradients from the "puffing" process. We use published results from ten Local Group dwarf galaxies to show that a similar relationship between age and stellar metallicity-gradient strength exists among real dwarfs. This suggests that observed stellar metallicity gradients may be driven largely by the baryon/feedback cycle rather than by external environmental effects.Comment: 14 pages, 13 figures, submitted to MNRA

Pain as a First Manifestation of Paraneoplastic Neuropathies: A Systematic Review and Meta-Analysis.

INTRODUCTION: Paraneoplastic neurological syndromes (PNS) consist of a heterogeneous group of neurological disorders triggered by cancer. The aim of this systematic review is to estimate the reported prevalence of pain in patients with paraneoplastic peripheral neuropathy (PPN). METHODS: A systematic computer-based literature search was conducted on PubMed database. RESULTS: Our search strategy resulted in the identification of 126 articles. After the eligibility assessment, 45 papers met the inclusion criteria. Full clinical and neurophysiological data were further extracted and involved 92 patients with PPN (54.5% males, mean age 60.0 ± 12.2 years). The commonest first manifestation of PPN is sensory loss (67.4%), followed by pain (41.3%), weakness (22.8%), and sensory ataxia (20.7%). In 13.0% of the cases, pain was the sole first manifestation of the PPN. During the course of the PPN, 57.6% of the patients may experience pain secondary to the neuropathy. CONCLUSIONS: Pain is very prevalent within PPN. Pain specialists should be aware of this. Detailed history-taking, full clinical examination, and requesting nerve conduction studies might lead to an earlier diagnosis of an underlying malignancy

Anti-Hu antibodies activate enteric and sensory neurons.

IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-β-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3 antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA. Ca(++) imaging experiments confirmed activation of enteric neurons but not enteric glia. These findings demonstrate a direct excitatory action of ANNA-1, in particular anti-HuD, on visceral sensory and enteric neurons, which involves nicotinic and P2X receptors. The results provide evidence for a novel link between nerve activation and symptom generation in patients with antibody-mediated gut dysfunction

Topological Analysis of MAPK Cascade for Kinetic ErbB Signaling

Ligand-induced homo- and hetero-dimer formation of ErbB receptors results in different biological outcomes irrespective of recruitment and activation of similar effector proteins. Earlier experimental research indicated that cells expressing both EGFR (epidermal growth factor receptor) and the ErbB4 receptor (E1/4 cells) induced E1/4 cell-specific B-Raf activation and higher extracellular signal-regulated kinase (ERK) activation, followed by cellular transformation, than cells solely expressing EGFR (E1 cells) in Chinese hamster ovary (CHO) cells. Since our experimental data revealed the presence of positive feedback by ERK on upstream pathways, it was estimated that the cross-talk/feedback pathway structure of the Raf-MEK-ERK cascade might affect ERK activation dynamics in our cell system. To uncover the regulatory mechanism concerning the ERK dynamics, we used topological models and performed parameter estimation for all candidate structures that possessed ERK-mediated positive feedback regulation of Raf. The structure that reliably reproduced a series of experimental data regarding signal amplitude and duration of the signaling molecules was selected as a solution. We found that the pathway structure is characterized by ERK-mediated positive feedback regulation of B-Raf and B-Raf-mediated negative regulation of Raf-1. Steady-state analysis of the estimated structure indicated that the amplitude of Ras activity might critically affect ERK activity through ERK-B-Raf positive feedback coordination with sustained B-Raf activation in E1/4 cells. However, Rap1 that positively regulates B-Raf activity might be less effective concerning ERK and B-Raf activity. Furthermore, we investigated how such Ras activity in E1/4 cells can be regulated by EGFR/ErbB4 heterodimer-mediated signaling. From a sensitivity analysis of the detailed upstream model for Ras activation, we concluded that Ras activation dynamics is dominated by heterodimer-mediated signaling coordination with a large initial speed of dimerization when the concentration of the ErbB4 receptor is considerably high. Such characteristics of the signaling cause the preferential binding of the Grb2-SOS complex to heterodimer-mediated signaling molecules

Axonal Regeneration and Neuronal Function Are Preserved in Motor Neurons Lacking ß-Actin In Vivo

The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA), suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO) to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo