Positively Correlated miRNA-miRNA Regulatory Networks in Mouse Frontal Cortex During Early Stages of Alcohol Dependence

Although the study of gene regulation via the action of specific microRNAs (miRNAs) has experienced a boom in recent years, the analysis of genome-wide interaction networks among miRNAs and respective targeted mRNAs has lagged behind. MicroRNAs simultaneously target many transcripts and fine-tune the expression of genes through cooperative/combinatorial targeting. Therefore, they have a large regulatory potential that could widely impact development and progression of diseases, as well as contribute unpredicted collateral effects due to their natural, pathophysiological, or treatment-induced modulation. We support the viewpoint that whole mirnome-transcriptome interaction analysis is required to better understand the mechanisms and potential consequences of miRNA regulation and/or deregulation in relevant biological models. In this study, we tested the hypotheses that ethanol consumption induces changes in miRNA-mRNA interaction networks in the mouse frontal cortex and that some of the changes observed in the mouse are equivalent to changes in similar brain regions from human alcoholics. Results: miRNA-mRNA interaction networks responding to ethanol insult were identified by differential expression analysis and weighted gene coexpression network analysis (WGCNA). Important pathways (coexpressed modular networks detected by WGCNA) and hub genes central to the neuronal response to ethanol are highlighted, as well as key miRNAs that regulate these processes and therefore represent potential therapeutic targets for treating alcohol addiction. Importantly, we discovered a conserved signature of changing miRNAs between ethanol-treated mice and human alcoholics, which provides a valuable tool for future biomarker/diagnostic studies in humans. We report positively correlated miRNA-mRNA expression networks that suggest an adaptive, targeted miRNA response due to binge ethanol drinking. Conclusions: This study provides new evidence for the role of miRNA regulation in brain homeostasis and sheds new light on current understanding of the development of alcohol dependence. To our knowledge this is the first report that activated expression of miRNAs correlates with activated expression of mRNAs rather than with mRNA downregulation in an in vivo model. We speculate that early activation of miRNAs designed to limit the effects of alcohol-induced genes may be an essential adaptive response during disease progression.NIAAA 5R01AA012404, 5P20AA017838, 5U01AA013520, P01AA020683, 5T32AA007471-24/25Waggoner Center for Alcohol and Addiction Researc

A Blue Tilt in the Globular Cluster System of the Milky Way-like Galaxy NGC 5170

Here we present HST/ACS imaging, in the B and I bands, of the edge-on Sb/Sc galaxy NGC 5170. Excluding the central disk region region, we detect a 142 objects with colours and sizes typical of globular clusters (GCs). Our main result is the discovery of a `blue tilt' (a mass-metallicity relation), at the 3sigma level, in the metal-poor GC subpopulation of this Milky Way like galaxy. The tilt is consistent with that seen in massive elliptical galaxies and with the self enrichment model of Bailin & Harris. For a linear mass-metallicity relation, the tilt has the form Z ~ L^{0.42 +/- 0.13}. We derive a total GC system population of 600 +/- 100, making it much richer than the Milky Way. However when this number is normalised by the host galaxy luminosity or stellar mass it is similar to that of M31. Finally, we report the presence of a potential Ultra Compact Dwarf of size ~ 6 pc and luminosity M_I ~ -12.5, assuming it is physically associated with NGC 5170.Comment: Accepted for publication in MNRAS, 11 pages, 10 figure

Deriving Metallicities From the Integrated Spectra of Extragalactic Globular Clusters Using the Near-Infrared Calcium Triplet

The Ca triplet (CaT) feature in the near-infrared has been employed as a metallicity indicator for individual stars as well as integrated light of Galactic globular clusters (GCs) and galaxies with varying degrees of success, and sometimes puzzling results. Using the DEIMOS multi-object spectrograph on Keck we obtain a sample of 144 integrated light spectra of GCs around the brightest group galaxy NGC 1407 to test whether the CaT index can be used as a metallicity indicator for extragalactic GCs. Different sets of single stellar population models make different predictions for the behavior of the CaT as a function of metallicity. In this work, the metallicities of the GCs around NGC 1407 are obtained from CaT index values using an empirical conversion. The measured CaT/metallicity distributions show unexpected features, the most remarkable being that the brightest red and blue GCs have similar CaT values despite their large difference in mean color. Suggested explanations for this behavior in the NGC 1407 GC system are: 1) the CaT may be affected by a population of hot blue stars, 2) the CaT may saturate earlier than predicted by the models, and/or 3) color may not trace metallicity linearly. Until these possibilities are understood, the use of the CaT as a metallicity indicator for the integrated spectra of extragalactic GCs will remain problematic.Comment: 14 pages, 18 figures, accepted for publication in A

Spectra of globular clusters in the Sombrero galaxy: evidence for spectroscopic metallicity bimodality

We present a large sample of over 200 integrated-light spectra of confirmed globular clusters (GCs) associated with the Sombrero (M104) galaxy taken with the DEIMOS instrument on the Keck telescope. A significant fraction of the spectra have signal-to-noise levels high enough to allow measurements of GC metallicities using the method of Brodie & Huchra (1990). We find a distribution of spectroscopic metallicities ranging from -2.2 < [Fe/H] < +0.1 that is bimodal, with peaks at [Fe/H] ~ -1.4 and -0.6. Thus the GC system of the Sombrero galaxy, like a few other galaxies now studied in detail, reveals a bimodal spectroscopic metallicity distribution supporting the long-held belief that colour bimodality reflects two metallicity subpopulations. This further suggests that the transformation from optical colour to metallicity for old stellar populations, such as GCs, is not strongly non-linear. We also explore the radial and magnitude distribution with metallicity for GC subpopulations but small number statistics prevent any clear trends in these distributions.Comment: 18 pages, 10 figures, 3 tables, MNRAS accepte

Forecast for Military Systems Using Electronic Digital Computers

Many plans are now being considered for the military use of information systems built around electronic digital computers. Such systems appear unique in their ability to process and evaluate information sufficiently rapidly for modern high-speed military operations. The advantages gained when digital information systems make possible the better integration and more effective use of other military equipment should more than justify the diversion of men and resources to digital information system development. An approximate estimate has been made of the time and cost to bring such information systems to useful military realization. This forecast shows a period of fifteen years and a research and development cost, including field testing and trial operation, of two billion dollars ($2,000,000,000) to bring these systems to an operational status. An equal or greater production program would follow for equipping the Military Services with production equipment. Compensating adjustments in completion time and total cost can be made to meet military necessity. Such a program would require an active training plan to provide necessary personnel. An initial investigation requiring four years and sixty-five million dollars ($65,000,000) would provide tho necessary information on which the importance and feasibility of the complete program could be judged

The SLUGGS Survey: Globular cluster system kinematics and substructure in NGC 4365

We present a kinematic analysis of the globular cluster (GC) system of the giant elliptical galaxy NGC 4365 and find several distinct kinematic substructures. This analysis is carried out using radial velocities for 269 GCs, obtained with the DEIMOS instrument on the Keck II telescope as part of the SAGES Legacy Unifying Globulars and Galaxies Survey (SLUGGS). We find that each of the three (formerly identified) GC colour subpopulations reveal distinct rotation properties. The rotation of the green GC subpopulation is consistent with the bulk of NGC 4365's stellar light, which `rolls' about the photometric major axis. The blue and red GC subpopulations show `normal' rotation about the minor axis. We also find that the red GC subpopulation is rotationally dominated beyond 2.5 arcmin (~17 kpc) and that the root mean squared velocity of the green subpopulation declines sharply with radius suggesting a possible bias towards radial orbits relative to the other GC subpopulations. Additionally, we find a population of low velocity GCs that form a linear structure running from the SW to the NE across NGC 4365 which aligns with the recently reported stellar stream towards NGC 4342. These low velocity GCs have g'-i' colours consistent with the overall NGC 4365 GC system but have velocities consistent with the systemic velocity of NGC 4342. We discuss the possible formation scenarios for the three GC subpopulations as well as the possible origin of the low velocity GC population.Comment: 15 pages, 12 figures, accepted for publication in MNRAS. For more information on "The SLUGGS Survey" see: http://sluggs.swin.edu.au

The SLUGGS Survey: Calcium Triplet-based Spectroscopic Metallicities for Over 900 Globular Clusters

Although the colour distribution of globular clusters in massive galaxies is well known to be bimodal, the spectroscopic metallicity distribution has been measured in only a few galaxies. After redefining the calcium triplet index-metallicity relation, we use our relation to derive the metallicity of 903 globular clusters in 11 early-type galaxies. This is the largest sample of spectroscopic globular cluster metallicities yet assembled. We compare these metallicities with those derived from Lick indices finding good agreement. In 6 of the 8 galaxies with sufficient numbers of high quality spectra we find bimodality in the spectroscopic metallicity distribution. Our results imply that most massive early-type galaxies have bimodal metallicity, as well as colour, distributions. This bimodality suggests that most massive galaxies early-type galaxies experienced two periods of star formation.Comment: 23 pages, 13 figures. Accepted for publication in MNRAS. For more information about the SLUGGS Survey please see http://sluggs.swin.edu.a