Untargeted metabolomic analysis of Rat neuroblastoma cells as a model system to study the biochemical effects of the acute administration of methamphetamine

Methamphetamine is an illicit psychostimulant drug that is linked to a number of diseases of the nervous system. The downstream biochemical effects of its primary mechanisms are not well understood, and the objective of this study was to investigate whether untargeted metabolomic analysis of an in vitro model could generate data relevant to what is already known about this drug. Rat B50 neuroblastoma cells were treated with 1 mM methamphetamine for 48 h, and both intracellular and extracellular metabolites were profiled using gas chromatography–mass spectrometry. Principal component analysis of the data identified 35 metabolites that contributed most to the difference in metabolite profiles. Of these metabolites, the most notable changes were in amino acids, with significant increases observed in glutamate, aspartate and methionine, and decreases in phenylalanine and serine. The data demonstrated that glutamate release and, subsequently, excitotoxicity and oxidative stress were important in the response of the neuronal cell to methamphetamine. Following this, the cells appeared to engage amino acid-based mechanisms to reduce glutamate levels. The potential of untargeted metabolomic analysis has been highlighted, as it has generated biochemically relevant data and identified pathways significantly affected by methamphetamine. This combination of technologies has clear uses as a model for the study of neuronal toxicology

Are the black hole masses in Narrow Line Seyfert 1 galaxies actually small?

Narrow Line Seyfert 1 galaxies (NLS1s) are generally considered peculiar objects among the broad class of Type 1 active galactic nuclei, due to the relatively small width of the broad lines, strong X-ray variability, soft X-ray continua, weak [OIII], and strong FeII line intensities. The mass M_BH of the central massive black hole (MBH) is claimed to be lighter than expected from known MBH-host galaxy scaling relations, while the accretion rate onto the MBH larger than the average value appropriate to Seyfert 1 galaxies. In this Letter, we show that NLS1 peculiar M_BH and L/L_Edd turn out to be fairly standard, provided that the broad line region is allowed to have a disc-like, rather than isotropic, geometry. Assuming that NLS1s are rather ``normal'' Seyfert 1 objects seen along the disc axis, we could estimate the typical inclination angles from the fraction of Seyfert 1 classified as NLS1s, and compute the geometrical factor relating the observed FWHM of broad lines to the virial mass of the MBH. We show that the geometrical factor can fully account for the "black hole mass deficit" observed in NLS1s, and that L/L_Edd is (on average) comparable to the value of the more common broad line Seyfert 1 galaxies.Comment: 5 pages, 3 figures. Accepted for publication in MNRAS Letters. Wrong version was uploaded! Check for the correct one in the replacemen

Morphological alterations of small intestinal epithelium of calves caused by feeding soybean protein.

The objective of this experiment was to detect alterations of small intestinal mucosa due to incorporation of large amounts of soybean protein in milk replacers and to relate these alterations to calf performance

Evidence for feedback in action from the molecular gas content in the z~1.6 outflowing QSO XID2028

Gas outflows are believed to play a pivotal role in shaping galaxies, as they regulate both star formation and black hole growth. Despite their ubiquitous presence, the origin and the acceleration mechanism of such powerful and extended winds is not yet understood. Direct observations of the cold gas component in objects with detected outflows at other wavelengths are needed to assess the impact of the outflow on the host galaxy interstellar medium (ISM). We observed with the Plateau de Bure Interferometer an obscured quasar at z~1.5, XID2028, for which the presence of an ionised outflow has been unambiguously signalled by NIR spectroscopy. The detection of CO(3-2) emission in this source allows us to infer the molecular gas content and compare it to the ISM mass derived from the dust emission. We then analyze the results in the context of recent insights on scaling relations, which describe the gas content of the overall population of star-forming galaxies at a similar redshifts. The Star formation efficiency (~100) and gas mass (M_gas=2.1-9.5x10^{10} M_sun) inferred from the CO(3-2) line depend on the underlying assumptions on the excitation of the transition and the CO-to-H2 conversion factor. However, the combination of this information and the ISM mass estimated from the dust mass suggests that the ISM/gas content of XID2028 is significantly lower than expected for its observed M⋆, sSFR and redshift, based on the most up-to-date calibrations (with gas fraction <20% and depletion time scale <340 Myr). Overall, the constraints we obtain from the far infrared and millimeter data suggest that we are observing QSO feedback able to remove the gas from the host

Active Galactic Nuclei in Dusty Starbursts at z = 2: Feedback Still to Kick in

We investigate a sample of 152 dusty sources at 1.5\uf0a0&lt;\uf0a0z\uf0a0&lt;\uf0a02.5 to understand the connection of enhanced star formation rate (SFR) and black hole accretion rate. The sources are Herschel-selected, having stellar masses M*\uf0a0&gt;\uf0a01010Me and SFR ( 3c100\u20131000Me yr 121) elevated (&gt;4 7) above the star-forming \u201cmain sequence,\u201d classifying them as starbursts (SBs). Through a multiwavelength fitting approach (including a dusty torus component), we divided the sample into active SBs (dominated by an active galactic nucleus (AGN) emission, SBs-AGN, 3c23% of the sample) and purely star-forming SBs (SBs-SFR). We visually inspected their Hubble Space Telescope/ultraviolet (UV) rest frame maps: SBs-SFR are generally irregular and composite systems; 3c50% of SBs-AGN are instead dominated by regular compact morphologies. We then found archival Atacama Large Millimeter/submillimeter Array continuum counterparts for 33 galaxies (12 SBs-AGN and 21 SBs-SFR). For these sources we computed dust masses, and, with standard assumptions, we also guessed total molecular gas masses. SBs turn into gas-rich systems ( fgas =Mgas/(Mgas\uf0a0+\uf0a0M*)\uf0a0;\uf0a020%\u201370%), and the gas fractions of the two SB classes are very similar ( fgas = 43% \ub1 4% and fgas = 42% \ub1 2%). Our results show that SBs are consistent with a mixture of: (1) highly star-forming merging systems (dominating the SBs-SFR) and (2) primordial galaxies, rapidly growing their M* together with their black hole (mainly the more compact SBs-AGN). Feedback effects have not yet reduced their fgas. Indeed, SBs at z\uf0a0=\uf0a02, with relatively low bolometric AGN luminosities in the range 1044\uf0a0&lt;\uf0a0Lbol(AGN)\uf0a0&lt;\uf0a01046 erg s 121 (compared to bright optical and X-ray quasars), are still relatively far from the epoch when the AGN feedback will quench the SFR in the host and will substantially depress the gas fractions

GOODS-Herschel: star formation, dust attenuation, and the FIR-radio correlation on the main sequence of star-forming galaxies up to z=4

We use deep panchromatic data sets in the GOODS-N field, from GALEX to the deepest Herschel far-infrared (FIR) and VLA radio continuum imaging, to explore the evolution of star-formation activity and dust attenuation properties of star-forming galaxies to z sime 4, using mass-complete samples. Our main results can be summarized as follows: (i) the slope of the star-formation rate–M* correlation is consistent with being constant sime0.8 up to z sime 1.5, while its normalization keeps increasing with redshift; (ii) for the first time we are able to explore the FIR–radio correlation for a mass-selected sample of star-forming galaxies: the correlation does not evolve up to z sime 4; (iii) we confirm that galaxy stellar mass is a robust proxy for UV dust attenuation in star-forming galaxies, with more massive galaxies being more dust attenuated. Strikingly, we find that this attenuation relation evolves very weakly with redshift, with the amount of dust attenuation increasing by less than 0.3 mag over the redshift range [0.5–4] for a fixed stellar mass; (iv) the correlation between dust attenuation and the UV spectral slope evolves with redshift, with the median UV slope becoming bluer with redshift. By z sime 3, typical UV slopes are inconsistent, given the measured dust attenuations, with the predictions of commonly used empirical laws. (v) Finally, building on existing results, we show that gas reddening is marginally larger (by a factor of around 1.3) than the stellar reddening at all redshifts probed. Our results support a scenario where the ISM conditions of typical star-forming galaxies evolve with redshift, such that at z ≥ 1.5 Main Sequence galaxies have ISM conditions moving closer to those of local starbursts

Bulge growth through disk instabilities in high-redshift galaxies

The role of disk instabilities, such as bars and spiral arms, and the associated resonances, in growing bulges in the inner regions of disk galaxies have long been studied in the low-redshift nearby Universe. There it has long been probed observationally, in particular through peanut-shaped bulges. This secular growth of bulges in modern disk galaxies is driven by weak, non-axisymmetric instabilities: it mostly produces pseudo-bulges at slow rates and with long star-formation timescales. Disk instabilities at high redshift (z>1) in moderate-mass to massive galaxies (10^10 to a few 10^11 Msun of stars) are very different from those found in modern spiral galaxies. High-redshift disks are globally unstable and fragment into giant clumps containing 10^8-10^9 Msun of gas and stars each, which results in highly irregular galaxy morphologies. The clumps and other features associated to the violent instability drive disk evolution and bulge growth through various mechanisms, on short timescales. The giant clumps can migrate inward and coalesce into the bulge in a few 10^8 yr. The instability in the very turbulent media drives intense gas inflows toward the bulge and nuclear region. Thick disks and supermassive black holes can grow concurrently as a result of the violent instability. This chapter reviews the properties of high-redshift disk instabilities, the evolution of giant clumps and other features associated to the instability, and the resulting growth of bulges and associated sub-galactic components.Comment: 37 pages, 9 figures. Invited refereed review to appear in "Galactic Bulges", E. Laurikainen, D. Gadotti, R. Peletier (eds.), Springe

The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake

We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms

The Quasar Feedback Survey: characterising CO excitation in quasar host galaxies

We present a comprehensive study of the molecular gas properties of 17 Type 2 quasars at $z$10^{42.1}$$\rm ergs^{-1}$), selected by their high [OIII] luminosities and displaying a large diversity of radio jet properties, but dominated by LIRG-like galaxies. With these data, we are able to investigate the impact of AGN and AGN feedback mechanisms on the global molecular interstellar medium. Using APEX and ALMA ACA observations, we measure the total molecular gas content using the CO(1-0) emission and homogeneously sample the CO spectral line energy distributions (SLEDs), observing CO transitions (J$_{up}$= 1, 2, 3, 6, 7). We observe high$r_{21}$ratios (r$_{21}$= L'$_{CO(2-1)}$/L'$_{CO(1-0)}$) with a median$r_{21}$= 1.06, similar to local (U)LIRGs (with$r_{21}$$\sim$1) and higher than normal star-forming galaxies (with r$_{21}$$\sim$0.65). Despite the high$r_{21} values, for the 7 targets with the required data we find low excitation in CO(6-5) & CO(7-6) (r_{61}$and$r_{62}$ < 0.6 in all but one target), unlike high redshift quasars in the literature, which are far more luminous and show higher line ratios. The ionised gas traced by [OIII] exhibit systematically higher velocities than the molecular gas traced by CO. We conclude that any effects of quasar feedback (e.g. via outflows and radio jets) do not have a significant instantaneous impact on the global molecular gas content and excitation and we suggest that it only occurs on more localised scales.Comment: 32 pages (20 in the main body of the paper and 12 in the appendix), 28 figures (10 in main body of paper and 18 in appendix) Accepted for publication in MNRAS. Data available at https://doi.org/10.25405/data.ncl.2431250

Black Holes in the Early Universe

The existence of massive black holes was postulated in the sixties, when the first quasars were discovered. In the late nineties their reality was proven beyond doubt, in the Milky way and a handful nearby galaxies. Since then, enormous theoretical and observational efforts have been made to understand the astrophysics of massive black holes. We have discovered that some of the most massive black holes known, weighing billions of solar masses, powered luminous quasars within the first billion years of the Universe. The first massive black holes must therefore have formed around the time the first stars and galaxies formed. Dynamical evidence also indicates that black holes with masses of millions to billions of solar masses ordinarily dwell in the centers of today's galaxies. Massive black holes populate galaxy centers today, and shone as quasars in the past; the quiescent black holes that we detect now in nearby bulges are the dormant remnants of this fiery past. In this review we report on basic, but critical, questions regarding the cosmological significance of massive black holes. What physical mechanisms lead to the formation of the first massive black holes? How massive were the initial massive black hole seeds? When and where did they form? How is the growth of black holes linked to that of their host galaxy? Answers to most of these questions are work in progress, in the spirit of these Reports on Progress in Physics.Comment: Reports on Progress in Physics, in pres