The M33 Globular Cluster System with PAndAS Data: The Last Outer Halo Cluster?

We use CFHT/MegaCam data to search for outer halo star clusters in M33 as part of the Pan-Andromeda Archaeological Survey (PAndAS). This work extends previous studies out to a projected radius of 50 kpc and covers over 40 square degrees. We find only one new unambiguous star cluster in addition to the five previously known in the M33 outer halo (10 kpc <= r <= 50 kpc). Although we identify 2440 cluster candidates of various degrees of confidence from our objective image search procedure, almost all of these are likely background contaminants, mostly faint unresolved galaxies. We measure the luminosity, color and structural parameters of the new cluster in addition to the five previously-known outer halo clusters. At a projected radius of 22 kpc, the new cluster is slightly smaller, fainter and redder than all but one of the other outer halo clusters, and has g' ~ 19.9, (g'-i') ~ 0.6, concentration parameter c ~ 1.0, a core radius r_c ~ 3.5 pc, and a half-light radius r_h ~ 5.5 pc. For M33 to have so few outer halo clusters compared to M31 suggests either tidal stripping of M33's outer halo clusters by M31, or a very different, much calmer accretion history of M33.Comment: 37 pages, 9 figures. Accepted by the Astrophysical Journa

The RR Lyrae Distance Scale

We review seven methods of measuring the absolute magnitude M_V of RR Lyrae stars in light of the Hipparcos mission and other recent developments. We focus on identifying possible systematic errors and rank the methods by relative immunity to such errors. For the three most robust methods, statistical parallax, trigonometric parallax, and cluster kinematics, we find M_V (at [Fe/H] = -1.6) of 0.77 +/- 0.13, 0.71 +/- 0.15, 0.67 +/- 0.10. These methods cluster consistently around 0.71 +/- 0.07. We find that Baade-Wesselink and theoretical models both yield a broad range of possible values (0.45-0.70 and 0.45-0.65) due to systematic uncertainties in the temperature scale and input physics. Main-sequence fitting gives a much brighter M_V = 0.45 +/- 0.04 but this may be due to a difference in the metallicity scales of the cluster giants and the calibrating subdwarfs. White-dwarf cooling-sequence fitting gives 0.67 +/- 0.13 and is potentially very robust, but at present is too new to be fully tested for systematics. If the three most robust methods are combined with Walker's mean measurement for 6 LMC clusters, V_{0,LMC} = 18.98 +/- 0.03 at [Fe/H] = -1.9, then mu_{LMC} = 18.33 +/- 0.08.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 21 pages including 1 table; uses Kluwer's crckapb.sty LaTeX style file, enclose

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

The Star Formation History and Dust Content in the Far Outer Disc of M31

We present a detailed analysis of two fields located 26 kpc (~5 scalelengths) from the centre of M31. One field samples the major axis populations--the Outer Disc field--while the other is offset by ~18' and samples the Warp in the stellar disc. The CMDs based on HST/ACS imaging reach old main-sequence turn-offs (~12.5 Gyr). We apply the CMD-fitting technique to the Warp field to reconstruct the star formation history (SFH). We find that after undergoing roughly constant SF until about 4.5 Gyr ago, there was a rapid decline in activity and then a ~1.5 Gyr lull, followed by a strong burst lasting 1.5 Gyr and responsible for 25% of the total stellar mass in this field. This burst appears to be accompanied by a decline in metallicity which could be a signature of the inflow of metal-poor gas. The onset of the burst (~3 Gyr ago) corresponds to the last close passage of M31 and M33 as predicted by detailed N-body modelling, and may have been triggered by this event. We reprocess the deep M33 outer disc field data of Barker et al. (2011) in order to compare consistently-derived SFHs. This reveals a similar duration burst that is exactly coeval with that seen in the M31 Warp field, lending further support to the interaction hypothesis. The complex SFHs and the smoothly-varying age-metallicity relations suggest that the stellar populations observed in the far outer discs of both galaxies have largely formed in situ rather than migrated from smaller galactocentric radii. The strong differential reddening affecting the CMD of the Outer Disc field prevents derivation of the SFH. Instead, we quantify this reddening and find that the fine-scale distribution of dust precisely follows that of the HI gas. This indicates that the outer HI disc of M31 contains a substantial amount of dust and therefore suggests significant metal enrichment in these parts, consistent with inferences from our CMD analysis.Comment: Abstract shortened. 17 pages, 12 figures (+ 6 pages & 5 figures in Appendix). MNRAS, in pres

Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin

We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]

In vivo photopharmacology with light-activated opioid drugs

Traditional methods for site-specific drug delivery in the brain are slow, invasive, and difficult to interface with recordings of neural activity. Here, we demonstrate the feasibility and experimental advantages of in vivo photopharmacology using "caged" opioid drugs that are activated in the brain with light after systemic administration in an inactive form. To enable bidirectional manipulations of endogenous opioid receptors in vivo, we developed photoactivatable oxymorphone (PhOX) and photoactivatable naloxone (PhNX), photoactivatable variants of the mu opioid receptor agonist oxymorphone and the antagonist naloxone. Photoactivation of PhOX in multiple brain areas produced local changes in receptor occupancy, brain metabolic activity, neuronal calcium activity, neurochemical signaling, and multiple pain- and reward-related behaviors. Combining PhOX photoactivation with optical recording of extracellular dopamine revealed adaptations in the opioid sensitivity of mesolimbic dopamine circuitry in response to chronic morphine administration. This work establishes a general experimental framework for using in vivo photopharmacology to study the neural basis of drug action

A Biomimetic C-Terminal Extension Strategy for Photocaging Amidated Neuropeptides.

Photoactivatable neuropeptides offer a robust stimulus-response relationship that can drive mechanistic studies into the physiological mechanisms of neuropeptidergic transmission. The majority of neuropeptides contain a C-terminal amide, which offers a potentially general site for installation of a C-terminal caging group. Here, we report a biomimetic caging strategy in which the neuropeptide C-terminus is extended via a photocleavable amino acid to mimic the proneuropeptides found in large dense-core vesicles. We explored this approach with four prominent neuropeptides: gastrin-releasing peptide (GRP), oxytocin (OT), substance P (SP), and cholecystokinin (CCK). C-terminus extension greatly reduced the activity of all four peptides at heterologously expressed receptors. In cell type-specific electrophysiological recordings from acute brain slices, subsecond flashes of ultraviolet light produced rapidly activating membrane currents via activation of endogenous G protein-coupled receptors. Subsequent mechanistic studies with caged CCK revealed a role for extracellular proteases in shaping the temporal dynamics of CCK signaling, and a striking switch-like, cell-autonomous anti-opioid effect of transient CCK signaling in hippocampal parvalbumin interneurons. These results suggest that C-terminus extension with a photocleavable linker may be a general strategy for photocaging amidated neuropeptides and demonstrate how photocaged neuropeptides can provide mechanistic insights into neuropeptide signaling that are inaccessible using conventional approaches

Improvements in task performance after practice are associated with scale-free dynamics of brain activity

202405 bcrcVersion of RecordOthersNational Science Foundation(National Science Foundation (NSF))TKF FoundationNational Institute on Alcohol Abuse and Alcoholism(United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA))Grossman Institute for Neuroscience, Quantitative Biology, and Human Behavior from the University of ChicagoPublishedC

In vivo photopharmacology with a caged mu opioid receptor agonist drives rapid changes in behavior.

Photoactivatable drugs and peptides can drive quantitative studies into receptor signaling with high spatiotemporal precision, yet few are compatible with behavioral studies in mammals. We developed CNV-Y-DAMGO-a caged derivative of the mu opioid receptor-selective peptide agonist DAMGO. Photoactivation in the mouse ventral tegmental area produced an opioid-dependent increase in locomotion within seconds of illumination. These results demonstrate the power of in vivo photopharmacology for dynamic studies into animal behavior