Hyperpolarized 13 C magnetic resonance spectroscopy detects toxin-induced neuroinflammation in mice.

Lipopolysaccharide (LPS) is a commonly used agent for induction of neuroinflammation in preclinical studies. Upon injection, LPS causes activation of microglia and astrocytes, whose metabolism alters to favor glycolysis. Assessing in vivo neuroinflammation and its modulation following therapy remains challenging, and new noninvasive methods allowing for longitudinal monitoring would be highly valuable. Hyperpolarized (HP) 13 C magnetic resonance spectroscopy (MRS) is a promising technique for assessing in vivo metabolism. In addition to applications in oncology, the most commonly used probe of [1-13 C] pyruvate has shown potential in assessing neuroinflammation-linked metabolism in mouse models of multiple sclerosis and traumatic brain injury. Here, we aimed to investigate LPS-induced neuroinflammatory changes using HP [1-13 C] pyruvate and HP 13 C urea. 2D chemical shift imaging following simultaneous intravenous injection of HP [1-13 C] pyruvate and HP 13 C urea was performed at baseline (day 0) and at days 3 and 7 post-intracranial injection of LPS (n = 6) or saline (n = 5). Immunofluorescence (IF) analyses were performed for Iba1 (resting and activated microglia/macrophages), GFAP (resting and reactive astrocytes) and CD68 (activated microglia/macrophages). A significant increase in HP [1-13 C] lactate production was observed at days 3 and 7 following injection, in the injected (ipsilateral) side of the LPS-treated mouse brain, but not in either the contralateral side or saline-injected animals. HP 13 C lactate/pyruvate ratio, without and with normalization to urea, was also significantly increased in the ipsilateral LPS-injected brain at 7 days compared with baseline. IF analyses showed a significant increase in CD68 and GFAP staining at 3 days, followed by increased numbers of Iba1 and GFAP positive cells at 7 days post-LPS injection. In conclusion, we can detect LPS-induced changes in the mouse brain using HP 13 C MRS, in alignment with increased numbers of microglia/macrophages and astrocytes. This study demonstrates that HP 13 C spectroscopy has substantial potential for providing noninvasive information on neuroinflammation

MOND vs. Newtonian dynamics in early-type galaxies. The case of NGC 4649 (M60)

Context: Regarding the significant interest in both dark matter and the application of MOND to early-type galaxies, we investigate the MOND theory by comparing its predictions, for models of constant mass-to-light ratio, with observational data of the early-type galaxy NGC 4649. Aims: We study whether measurements for NGC 3379 and NGC 1399 are typical of early-type systems and we test the assumption of a Newtonian constant M/L ratio underlying most of the published models. Methods: We employ the globular clusters of NGC 4649 as a mass tracer. The Jeans equation is calculated for both MOND and constant mass-to-light ratio assumptions. Spherical symmetry is assumed and the calculations are performed for both isotropic and anisotropic cases. Results: We found that both Jeans models with the assumption of a constant mass-to-light ratio and different MOND models provide good agreement with the observed values of the velocity dispersion. The most accurate fits of the velocity dispersion were obtained for the mass-to-light ratio in the B-band, which was equal to 7, implying that there is no need for significant amounts of dark matter in the outer parts (beyond 3 effective radii) of this galaxy. We also found that tangential anisotropies are most likely present in NGC 4649.Comment: 6 pages, 4 figure

Admission to hospital following head injury in England: Incidence and socio-economic associations

BACKGROUND: Head injury in England is common. Evidence suggests that socio-economic factors may cause variation in incidence, and this variation may affect planning for services to meet the needs of those who have sustained a head injury. METHODS: Socio-economic data were obtained from the UK Office for National Statistics and merged with Hospital Episodes Statistics obtained from the Department of Health. All patients admitted for head injury with ICD-10 codes S00.0–S09.9 during 2001–2 and 2002–3 were included and collated at the level of the extant Health Authorities (HA) for 2002, and Primary Care Trust (PCT) for 2003. Incidence was determined, and cluster analysis and multiple regression analysis were used to look at patterns and associations. Results: 112,718 patients were admitted during 2001–2 giving a hospitalised incidence rate for England of 229 per 100,000. This rate varied across the English HA's ranging from 91–419 per 100,000. The rate remained unchanged for 2002–3 with a similar magnitude of variation across PCT's. Three clusters of HA's were identified from the 2001–2 data; those typical of London, those of the Shire counties, and those of Other Urban authorities. Socio-economic factors were found to account for a high proportion of the variance in incidence for 2001–2. The same pattern emerged for 2002–3 at the PCT level. The use of public transport for travel to work is associated with a decreased incidence and lifestyle indicators, such as the numbers of young unemployed, increase the incidence. CONCLUSION: Head injury incidence in England varies by a factor of 4.6 across HA's and PCT's. Planning head injury related services at the local level thus needs to be based on local incidence figures rather than regional or national estimates. Socio-economic factors are shown to be associated with admission, including travel to work patterns and lifestyle indicators, which suggests that incidence is amenable to policy initiatives at the macro level as well as preventive programmes targeted at key groups

On the central stellar mass density and the inside-out growth of early-type galaxies

[Abridged] In this paper we derive the central stellar mass density within a fixed radius and the effective stellar mass density within the effective radius for a complete sample of 34 ETGs morphologically selected at 0.9<z_{spec}<2 and compare them with those derived for a sample of ~900 local ETGs in the same mass range. We find that the central stellar mass density of high-z ETGs spans just an order of magnitude and it is similar to the one of local ETGs as actually found in previous studies.However, we find that the effective stellar mass density of high-z ETGs spans three orders of magnitude, exactly as the local ETGs and that it is similar to the effective stellar mass density of local ETGs showing that it has not changed since z~1.5, in the last 9-10 Gyr. Thus, the wide spread of the effective stellar mass density observed up to z~1.5 must originate earlier, at z>2. Also, we show that the small scatter of the central mass density of ETGs compared to the large scatter of the effective mass density is simply a peculiar feature of the Sersic profile hence, independent of redshift and of any assembly history experienced by galaxies. Thus, it has no connection with the possible inside-out growth of ETGs. Finally, we find a tight correlation between the central stellar mass density and the total stellar mass of ETGs in the sense that the central mass density increases with mass as M^{~0.6}. This implies that the fraction of the central stellar mass of ETGs decreases with the mass of the galaxy. These correlations are valid for the whole population of ETGs considered independently of their redshift suggesting that they originate in the early-phases of their formation.Comment: 11 pages, 6 figures. Accepted for publication in MNRAS (MNRAS version

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

Families of dynamically hot stellar systems over ten orders of magnitude in mass

Dynamically hot stellar systems, whether star clusters or early-type galaxies, follow well-defined scaling relations over many orders of magnitudes in mass. These fundamental plane relations have been subject of several studies, which have been mostly confined to certain types of galaxies and/or star clusters so far. Here, we present a complete picture of hot stellar systems ranging from faint galaxies and star clusters of only a few hundred solar masses up to giant ellipticals (gEs) with 10^12 M_sun, in particular including large samples of compact ellipticals (cEs), ultra-compact dwarf galaxies (UCDs), dwarf ellipticals (dEs) of nearby galaxy clusters and Local Group ultra-faint dwarf spheroidals (dSphs). For all those stellar systems we show the effective radius-luminosity, effective radius-stellar mass, and effective mass surface density-stellar mass plane. Two families of hot stellar systems can be differentiated: the 'galaxian' family, ranging from gEs over Es and dEs to dSphs, and the 'star cluster' family, comprising globular clusters (GCs), UCDs and nuclear star clusters (NCs). Interestingly, massive ellipticals have a similar size-mass relation as cEs, UCDs and NCs, with a clear common boundary towards minimum sizes. No object of either family is located in the 'zone of avoidance' beyond this limit. Even the majority of early-type galaxies at high redshift obeys this relation. The sizes of dEs and dSphs as well as GCs barely vary with mass over several orders of magnitude. We use the constant galaxy sizes to derive the distances of several local galaxy clusters. Both, galaxies and star clusters, do not exceed a surface density of \Sigma_eff = 3.17*10^{10}*M^{-3/5} M_sun pc^{-2}, causing an orthogonal kink in the galaxy sequence for ellipticals more massive than 10^{11} M_sun. The densest stellar systems (within their effective radius) are nuclear star clusters. (abridged)Comment: 13 pages, 7 figures, accepted for publication in MNRAS. Errors for mean effective radii and related quantities in Table 3 corrected, references added and affiliation changed in the replaced versio

The VPOS: a vast polar structure of satellite galaxies, globular clusters and streams around the Milky Way

It has been known for a long time that the satellite galaxies of the Milky Way (MW) show a significant amount of phase-space correlation, they are distributed in a highly inclined Disc of Satellites (DoS). We have extended the previous studies on the DoS by analysing for the first time the orientations of streams of stars and gas, and the distributions of globular clusters within the halo of the MW. It is shown that the spatial distribution of MW globular clusters classified as young halo clusters (YH GC) is very similar to the DoS, while 7 of the 14 analysed streams align with the DoS. The probability to find the observed clustering of streams is only 0.3 per cent when assuming isotropy. The MW thus is surrounded by a vast polar structure (VPOS) of subsystems (satellite galaxies, globular clusters and streams), spreading from Galactocentric distances as small as 10 kpc out to 250 kpc. These findings demonstrate that a near-isotropic infall of cosmological sub-structure components onto the MW is essentially ruled out because a large number of infalling objects would have had to be highly correlated, to a degree not natural for dark matter sub-structures. The majority of satellites, streams and YH GCs had to be formed as a correlated population. This is possible in tidal tails consisting of material expelled from interacting galaxies. We discuss the tidal scenario for the formation of the VPOS, including successes and possible challenges. The potential consequences of the MW satellites being tidal dwarf galaxies are severe. If all the satellite galaxies and YH GCs have been formed in an encounter between the young MW and another gas-rich galaxy about 10-11 Gyr ago, then the MW does not have any luminous dark-matter substructures and the missing satellites problem becomes a catastrophic failure of the standard cosmological model.Comment: 21 pages, 8 figures, 2 tables. Accepted for publication in MNRAS. An animation of Figure 5 can be found at http://youtu.be/nUwxv-WGfH

The PN.S Elliptical Galaxy Survey: the dark matter in NGC 4494

We present new Planetary Nebula Spectrograph observations of the ordinary elliptical galaxy NGC 4494, resulting in positions and velocities of 255 PNe out to 7 effective radii (25 kpc). We also present new wide-field surface photometry from MMT/Megacam, and long-slit stellar kinematics from VLT/FORS2. The spatial and kinematical distributions of the PNe agree with the field stars in the region of overlap. The mean rotation is relatively low, with a possible kinematic axis twist outside 1 Re. The velocity dispersion profile declines with radius, though not very steeply, down to ~70 km/s at the last data point. We have constructed spherical dynamical models of the system, including Jeans analyses with multi-component LCDM-motivated galaxies as well as logarithmic potentials. These models include special attention to orbital anisotropy, which we constrain using fourth-order velocity moments. Given several different sets of modelling methods and assumptions, we find consistent results for the mass profile within the radial range constrained by the data. Some dark matter (DM) is required by the data; our best-fit solution has a radially anisotropic stellar halo, a plausible stellar mass-to-light ratio, and a DM halo with an unexpectedly low central density. We find that this result does not substantially change with a flattened axisymmetric model. Taken together with other results for galaxy halo masses, we find suggestions for a puzzling pattern wherein most intermediate-luminosity galaxies have very low concentration halos, while some high-mass ellipticals have very high concentrations. We discuss some possible implications of these results for DM and galaxy formation.Comment: 29 pages, 17 figures. MNRAS, accepte