Leucine-rich repeat kinase 2 (LRRK2): an update on the potential therapeutic target for Parkinson’s disease

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are a risk factor for and a cause of sporadic and familial Parkinson’s disease (PD), respectively. These mutations are some of the most common genetic contributors to PD and render the kinase hyperactive. Increasingly within the past decade, there has been substantial effort investigating LRRK2 as a target for therapeutics in preclinical studies, and currently, small-molecule inhibitors and antisense oligonucleotides are being assessed in clinical trials as therapies to reduce the toxic hyperactivity of its kinase and/or reduce total levels of the protein in healthy individuals and people with PD

The Cuspy LINER Nucleus of the S0/a Galaxy NGC 2681

The nucleus of the bulge-dominated, multiply-barred S0/a galaxy NGC 2681 is studied in detail, using high resolution Hubble Space Telescope FOC and NICMOS imaging and FOS spectroscopy. The ionised gas central velocity dispersion is found to increase by a factor ~2 when narrowing the aperture from R~1.5" (ground) to R~0.1" (FOS). Dynamical modeling of these velocity dispersions suggests that NGC 2681 does host a supermassive black hole (BH) for which one can estimate a firm mass upper limit M_BH < 6*10^7 Solar Masses. This upper limit is consistent with the relation between the central BH mass and velocity dispersion M_BH - sigma known for other galaxies. The emission line ratios place the nucleus of NGC 2681 among LINERs. It is likely that the emission line region comes from a rather mild, but steady, feeding of gas to the central BH in this galaxy. The inner stellar population lacks any measurable color gradient (to a radius of 0.6 kpc) from the infrared to the ultraviolet, consistently with FOC, FOS and IUE data, all indicating that this system underwent a starburst ~1 Gyr ago that encompassed its whole interior, down to its very center. The most likely source of such a widely-distributed starburst is the dumping of tidally-extruded gas from a galaxy neighbor. If so, then NGC 2681 can be considered as the older brother of M82, seen face-on as opposed to the edge-on view we have for M82.Comment: 25 pages, LaTeX, with 10 PostScript figures, to appear in The Astrophysical Journa

Origin of Two Distinct Populations in Dwarf Spheroidal Galaxies

We study the chemical and kinematic properties of the first galaxies which formed at a high redshift, using high resolution cosmological numerical simulations, and compared them with the recent observational results for the Sculptor dwarf spheroidal galaxy by Tolstoy et al., who found two distinct stellar populations: the lower metallicity stars are more spatially extended and possess a higher velocity dispersion than the higher metallicity stars. Our calculations reproduce these observations as the result of a steep metallicity gradient, within a single populations, induced by dissipative collapse of the gas component. We also predict strong [N/O] enhancements in the lowest metallicity stars in dwarf spheroidals, due to the preferential retention of ejected gas from intermediate mass stars, compared to Type II supernovae.Comment: 11 pages, 10 figures, accepted for publication in Ap

Halos of Spiral Galaxies. III. Metallicity Distributions

(Abriged) We report results of a campaign to image the stellar populations in the halos of highly inclined spiral galaxies, with the fields roughly 10 kpc (projected) from the nuclei. We use the F814W (I) and F606W (V) filters in the Wide Field Planetary Camera 2, on board the Hubble Space telescope. Extended halo populations are detected in all galaxies. The color-magnitude diagrams appear to be completely dominated by giant-branch stars, with no evidence for the presence of young stellar populations in any of the fields. We find that the metallicity distribution functions are dominated by metal-rich populations, with a tail extending toward the metal poor end. To first order, the overall shapes of the metallicity distribution functions are similar to what is predicted by simple, single-component model of chemical evolution with the effective yields increasing with galaxy luminosity. However, metallicity distributions significantly narrower than the simple model are observed for a few of the most luminous galaxies in the sample. It appears clear that more luminous spiral galaxies also have more metal-rich stellar halos. The increasingly significant departures from the closed-box model for the more luminous galaxies indicate that a parameter in addition to a single yield is required to describe chemical evolution. This parameter, which could be related to gas infall or outflow either in situ or in progenitor dwarf galaxies that later merge to form the stellar halo, tends to act to make the metallicity distributions narrower at high metallicity.Comment: 20 pages, 8 figures (ApJ, in press

Leucine-rich repeat kinase 2 (LRRK2): an update on the potential therapeutic target for Parkinson's disease.

In this review, we will provide an update on the current status of drugs and other technologies that have emerged in recent years and provide an overview of their efficacy in ameliorating LRRK2 kinase activity and overall safety in animal models and humans. The growth of both target discovery and innovative drug design has sparked a lot of excitement for the future of how we treat Parkinson's disease. Given the immense focus on LRRK2 as a therapeutic target, it is expected within the next decade to determine its therapeutic properties, or lack thereof, for PD

Integrated Spectroscopy of Bulge Globular Clusters and Fields I. The Data Base and Comparison of Individual Lick Indices in Clusters and Bulge

We present a comprehensive spectroscopic study of the integrated light of metal-rich Galactic globular clusters and the stellar population in the Galactic bulge. We measure line indices which are defined by the Lick standard system and compare index strengths of the clusters and Galactic bulge. Both metal-rich globular clusters and the bulge are similar in most of the indices, except for the CN index. We find a significant enhancement in the CN/ index ratio in metal-rich globular clusters compared with the Galactic bulge. The mean iron index of the two metal-rich globular clusters NGC 6528 and NGC 6553 is comparable with the mean iron index of the bulge. Index ratios such as Mgb/, Mg2/, Ca4227/, and TiO/, are comparable in both stellar population indicating similar enhancements in individual elements which are traced by the indices. From the globular cluster data we fully empirically calibrate several metallicity-sensitive indices as a function of [Fe/H] and find tightest correlations for the Mg2 index and the composite [MgFe] index. We find that all indices show a similar behavior with galactocentric radius, except for the Balmer series, which show a large scatter at all radii. However, the scatter is entirely consistent with the cluster-to-cluster variations in the horizontal branch morphology.Comment: accepted for publication in A&A, 25 pages, incl. 10 figure

Why Are Radio-Galaxies Prolific Producers of Type Ia Supernovae?

An analysis of SNIa events in early type galaxies from the Cappellaro et al (1999) database provides conclusive evidence that the rate of type Ia Supernovae (SNe) in radio-loud galaxies is about 4 times higher than the rate measured in radio-quiet galaxies, i.e. SNIa-rate$(radio-loud galaxies) = 0.43^{+0.19}_{-0.14}h^2_{75}$ SNu as compared to SNIa-rate$(radio-quiet galaxies) = 0.11^{+0.06}_{-0.03}h^2_{75}$ SNu. The actual value of the enhancement is likely to be in the range $\sim 2-7$ (P$\sim 10^{-4}$). This finding puts on robust empirical grounds the results obtained by Della Valle & Panagia (2003) on the basis of a smaller sample of SNe. We analyse the possible causes of this result and conclude that the enhancement of SNIa explosion rate in radio-loud galaxies has the same origin as their being strong radio sources, but there is no causality link between the two phenomena. We argue that repeated episodes of interaction and/or mergers of early type galaxies with dwarf companions, on times-scale of about 1 Gyr, are responsible for inducing both strong radio activity observed in $\sim$14% of early type galaxies and to supply an adequate number of SNIa progenitors to the stellar population of ellipticals.Comment: 26 pages+6 figures, ApJ, in pres

Integrated Spectroscopy of Bulge Globular Clusters and Fields. II. Implications for stellar population models and elliptical galaxies

Synthetic Lick indices (e.g. Mg_2, Fe, etc.) of Simple Stellar Population (SSP) models are calibrated for the first time up to solar metallicity with a sample of Milky Way globular clusters (GCs) which includes the metal rich GCs of the Galactic bulge. This metallicity range is relevant to elliptical galaxies. It is shown that the Bulge GCs and integrated light follow the same correlation between Mg and Fe indices of elliptical galaxies, showing weaker Fe indices at given Mg indices with respect to models that assume solar-scaled abundances. This similarity is the robust empirical evidence for enhanced alpha/Fe ratios in the stellar populations of elliptical galaxies, since the globular clusters are independently known to be alpha-enhanced. The uniqueness of this alpha-overabundance solution is checked by exploring the whole range of model ingredients. We argue that the standard models reproduce the Mg-Fe correlation at low metallicities because the stellar templates used in the synthesis are the alpha-enhanced stars of the galactic Halo. These same models, however, fail to recover the Mg-Fe pattern of Bulge clusters and ellipticals at high metallicities because the high-metallicity templates are disk stars, which are not alpha-enhanced. The new SSP models by Thomas, Maraston & Bender (2002) which incorporate the dependence on alpha/Fe reproduce the Mg and Fe indices of GCs at all metallicities, with alpha/Fe=+0.3, which is in agreement with spectroscopic abundance determinations. The Balmer indices (Hbeta, Hdelta, Hgamma) are very well calibrated, provided the Horizontal Branch morphology is taken into account. In particular, we reproduce the Balmer lines of NGC 6388 and NGC 6441, which are metal-rich GCs with a tail of warm Horizontal Branch stars. {Abridged}Comment: 19 pages, 13 figures, Astronomy and Astrophysics in press. Only minor changes after the referee repor

The H Beta Index as an Age Indicator of Old Stellar Systems: The Effects of Horizontal-Branch Stars

The strength of the H$\beta$ index has been computed for the integrated spectra of model globular clusters from the evolutionary population synthesis. These models take into account, for the first time, the detailed systematic variation of horizontal-branch (HB) morphology with age and metallicity. Our models show that the H$\beta$ index is significantly affected by the presence of blue HB stars. Because of the contribution from blue HB stars, the H$\beta$ does not monotonically decrease as metallicity increases at a given age. Instead, it reaches a maximum strength when the distribution of HB stars is centered around 9500 K, the temperature where the H$\beta$ index becomes strongest. Our models indicate that the strength of the H$\beta$ index increases as much as 0.75 {\AA} due to the presence of blue HB stars. The comparison of the recent Keck observations of the globular cluster system in the Milky Way Galaxy with those in giant elliptical galaxies, NGC 1399 and M87, shows a systematic shift in the H$\beta$ against metallicity plane. Our models suggest that this systematic difference is understood if the globular cluster systems in giant elliptical galaxies are several billion years older, in the mean, than the Galactic counterpart. Further observations of globular cluster systems in the external galaxies from the large ground-based telescopes and space UV facilities will enable to clarify whether this difference is indeed due to the age difference or other explanations are also possible.Comment: 21 pages, 8 figures, Accepted for publication in the Astronomical Journal, August 2000 issue, Postscript files are available at http://csaweb.yonsei.ac.kr/~hclee/Hbet

Globular Clusters in the Magellanic Clouds.II: IR-Array Photometry for 12 Globulars and Contributions to the Integrated Cluster Light

We report the results of the observations in the JHK bands of 12 globular clusters in the LMC, and present CMDs down to K=16 for about 450 stars. We merge the data with the BV ones presented in paper I and use the merged data to study the evolution of integrated magnitudes and colours of SSPs. We find that the AGB contributes about 60 percent of integrated clusters light in K, while the contribution from RGB is correlated with the age of the cluster. The age at which the first appearance of the RGB takes place depends on the models adopted ranging from about 600 Myr in the "classical" models to about 1.5 Gyr with the "overshooting" models. Both models give the same fractional contribution of the RGB to the cluster light, in agreement with the Fuel Consumption Theorem. The overall picture is consistent with the early conclusions of Persson et al. 1983 and Frogel et al. 1990 that J-K colour is driven by AGB stars, V-K is controlled by AGB and RGB stars and B-V is partially influenced by the whole population redder than the RGB clump, but is strongly dependent on the fading and reddening of the TO stars with age.Comment: 26 pages, 15 figures available on request, uuencoded compressed postscript file with tables included, BAP 08-1994-021-OA