Coupling of D2R Short but not D2R Long receptor isoform to the Rho/ROCK signaling pathway renders striatal neurons vulnerable to mutant huntingtin.

Huntington's disease, an inherited neurodegenerative disorder, results from abnormal polyglutamine extension in the N-terminal region of the huntingtin protein. This mutation causes preferential degeneration of striatal projection neurons. We previously demonstrated, in vitro, that dopaminergic D2 receptor stimulation acted in synergy with expanded huntingtin to increase aggregates formation and striatal death through activation of the Rho/ROCK signaling pathway. In vivo, in a lentiviral-mediated model of expanded huntingtin expression in the rat striatum, we found that the D2 antagonist haloperidol protects striatal neurons against expanded huntingtin-mediated toxicity. Two variant transcripts are generated by alternative splicing of the of D2 receptor gene, the D2R-Long and the D2R-Short, which are thought to play different functional roles. We show herein that overexpression of D2R-Short, but not D2R-Long in cell lines is associated with activation of the RhoA/ROCK signaling pathway. In striatal neurons in culture, the selective D2 agonist Quinpirole triggers phosphorylation of cofilin, a downstream effector of ROCK, which is abrogated by siRNAs that knockdown both D2R-Long and D2R-Short, but not by siRNAs targeting D2R-Long alone. Aggregate formation and neuronal death induced by expanded huntingtin, were potentiated by Quinpirole. This D2 agonist-mediated effect was selectively inhibited by the siRNA targeting both D2R-Long and D2R-Short but not D2R-Long alone. Our data provide evidence for a specific coupling of D2R-Short to the RhoA/ROCK/cofilin pathway, and its involvement in striatal vulnerability to expanded huntingtin. A new route for targeting Rho-ROCK signaling in Huntington's disease is unraveled with our findings

Extended Star Formation and Molecular Gas in the Tidal Arms near NGC3077

We report the detection of ongoing star formation in the prominent tidal arms near NGC 3077 (member of the M 81 triplet). In total, 36 faint compact HII regions were identified, covering an area of ~4x6 kpc^2. Most of the HII regions are found at HI column densities above 1x10^21 cm^-2 (on scales of 200 pc), well within the range of threshold columns measured in normal galaxies. The HII luminosity function resembles the ones derived for other low-mass dwarf galaxies in the same group; we derive a total star formation rate of 2.6x10^-3 M_sun/yr in the tidal feature. We also present new high-resolution imaging of the molecular gas distribution in the tidal arm using CO observations obtained with the OVRO interferometer. We recover about one sixth of the CO flux (or M_H2~2x10^6 M_sun, assuming a Galactic conversion factor) originally detected in the IRAM 30m single dish observations, indicating the presence of a diffuse molecular gas component in the tidal arm. The brightest CO peak in the interferometer map (comprising half of the detected CO flux) is coincident with one of the brightest HII regions in the feature. Assuming a constant star formation rate since the creation of the tidal feature (presumably ~3x10^8 years ago), a total mass of ~7x10^5 M_sun has been transformed from gas into stars. Over this period, the star formation in the tidal arm has resulted in an additional enrichment of Delta(Z)>0.002. The reservoir of atomic and molecular gas in the tidal arm is ~3x10^8 M_sun, allowing star formation to continue at its present rate for a Hubble time. Such wide-spread, low-level star formation would be difficult to image around more distant galaxies but may be detectable through intervening absorption in quasar spectra.Comment: Accepted for publication in the Astronomical Journa

Observation of the Halo of NGC 3077 Near the "Garland" Region Using the Hubble Space Telescope

We report the detection of upper main sequence stars and red giant branch stars in the halo of an amorphous galaxy, NGC3077. The observations were made using Wide Field Planetary Camera~2 on board the Hubble Space Telescope. The red giant branch luminosity function in I-band shows a sudden discontinuity at I = 24.0 +- 0.1 mag. Identifying this with the tip of the red giant branch (TRGB), and adopting the calibration provided by Lee, Freedman, & Madore (1993) and the foreground extinction of A_B = 0.21 mag, we obtain a distance modulus of (m-M)_0 = 27.93 +- 0.14(random) +- 0.16(sys). This value agrees well with the distance estimates of four other galaxies in the M81 Group. In addition to the RGB stars, we observe a concentration of upper main sequence stars in the halo of NGC3077, which coincides partially with a feature known as the ``Garland''. Using Padua isochrones, these stars are estimated to be <150 Myrs old. Assuming that the nearest encounter between NGC3077 and M81 occurred 280 Myrs ago as predicted by the numerical simulations (Yun 1997), the observed upper main sequence stars are likely the results of the star formation triggered by the M81-NGC3077 tidal interaction.Comment: 15 pages, 8 figures. Accepted for publication in Astrophysical Journa

The Discovery of a Molecular Complex in the Tidal Arms near NGC 3077

We present the discovery of a giant molecular complex (r=350 pc, M_ vir=10^7 M_sun) in the tidal arms south-east of NGC 3077, a member of the M 81 triplet. The complex is clearly detected in the 12CO (J=1-0) transition at five independent positions. The position relative to NGC 3077, the systemic velocity (v_hel=14km/s) and the cloud averaged line width (15km/s) indicate that the object is not related to Galactic cirrus but is extragalactic. The tidal HI arm where the molecular complex is located has an total HI mass of M_HI=3x10^8 M_sun. This tidal material was presumably stripped off the outer parts of NGC 3077 during the closest encounter with M 81, about 3x10^8 years ago. After the complex detected along a torn-out spiral arm of M 81 by Brouillet et al., it is the second of its kind reported so far. Based on published optical observations, we have no evidence for on--going star formation in the newly detected molecular complex. Since the system has all the ingredients to form stars in the future, we speculate that it might eventually resemble the young dwarf galaxies in the M 81 group.Comment: 12 pages (including 3 figures), accepted for publication in the ApJ Letter

Tracing high density gas in M 82 and NGC 4038

We present the first detection of CS in the Antennae galaxies towards the NGC 4038 nucleus, as well as the first detections of two high-J (5-4 and 7-6) CS lines in the center of M 82. The CS(7-6) line in M 82 shows a profile that is surprisingly different to those of other low-J CS transitions we observed. This implies the presence of a separate, denser and warmer molecular gas component. The derived physical properties and the likely location of the CS(7-6) emission suggests an association with the supershell in the centre of M 82.Comment: 10 pages, 3 figures, ApJ Letter - ACCEPTE

Manual dexterity, but not cerebral palsy, predicts cognitive functioning after neonatal stroke

AIM: To disentangle the respective impacts of manual dexterity and cerebral palsy (CP) in cognitive functioning after neonatal arterial ischaemic stroke. METHOD: The population included 60 children (21 females, 39 males) with neonatal arterial ischaemic stroke but not epilepsy. The presence of CP was assessed clinically at the age of 7 years and 2 months (range 6y 11mo-7y 8mo) using the definition of the Surveillance of CP in Europe network. Standardized tests (Nine-Hole Peg Test and Box and Blocks Test) were used to quantify manual (finger and hand respectively) dexterity. General cognitive functioning was evaluated with the Wechsler Intelligence Scale for Children, Fourth Edition. Simple and multiple linear regression models were performed while controlling for socio-economic status, lesion side, and sex. RESULTS: Fifteen children were diagnosed with CP. In simple regression models, both manual dexterity and CP were associated with cognitive functioning (β=0.41 [p=0.002] and β=0.31 [p=0.019] respectively). However, in multiple regression models, manual dexterity was the only associated variable of cognitive functioning, whether or not a child had CP (β=0.35; p=0.007). This result was reproduced in models with other covariables (β=0.31; p=0.017). INTERPRETATION: As observed in typically developing children, manual dexterity is related to cognitive functioning in children having suffered a focal brain insult during the neonatal period. WHAT THIS PAPER ADDS: Manual dexterity predicts cognitive functioning after neonatal arterial ischaemic stroke. Correlations between manual dexterity and cognitive functioning occur irrespective of sex, lesion side, presence of cerebral palsy, and socio-economic status. Residual motor ability may support cognitive functioning

Atomic Carbon in M82: Physical conditions derived from simultaneous observations of the [CI] fine structure submillimeter wave transitions

We report the first extragalactic detection of the neutral carbon [CI] 3P2-3P1 fine structure line at 809 GHz. The line was observed towards M82 simultaneously with the 3P1-3P0 line at 492 GHz, providing a precise measurement of the J=2-1/J=1-0 integrated line ratio of 0.96 (on a [K km s^-1] -scale). This ratio constrains the [CI] emitting gas to have a temperature of at least 50 K and a density of at least 10^4 cm^-3. Already at this minimum temperature and density, the beam averaged CI-column density is large, 2.1 10^18 cm^-2, confirming the high CI/CO abundance ratio of approximately 0.5 estimated earlier from the 492 GHz line alone. We argue that the [CI] emission from M82 most likely arises in clouds of linear size around a few pc with a density of about 10^4 cm^-3 or slightly higher and temperatures of 50 K up to about 100 K.Comment: 4 pages, 2 figures, ApJL in press, postscript also available at ftp://apollo.ph1.uni-koeln.de/pub/stutzki/m82_pap.ps.gz e-mail-contact:[email protected]

The Molecular Interstellar Medium of the Local Group Dwarf NGC6822

Do molecular clouds collapse to form stars at the same rate in all environments? In large spiral galaxies, the rate of transformation of H2 into stars (hereafter SFE) varies little. However, the SFE in distant objects (z~1) is much higher than in the large spiral disks that dominate the local universe. Some small local group galaxies share at least some of the characteristics of intermediate-redshift objects, such as size or color. Recent work has suggested that the Star Formation Efficiency (SFE, defined as the SFRate per unit H2) in local Dwarf galaxies may be as high as in the distant objects. A fundamental difficulty in these studies is the independent measure of the H2 mass in metal-deficient environments. At 490 kpc, NGC6822 is an excellent choice for this study; it has been mapped in the CO(2-1) line using the multibeam receiver HERA on the 30 meter IRAM telescope, yielding the largest sample of giant molecular clouds (GMCs) in this galaxy. Despite the much lower metallicity, we find no clear difference in the properties of the GMCs in NGC 6822 and those in the Milky Way except lower CO luminosities for a given mass. Several independent methods indicate that the total H2 mass in NGC 6822 is about 5 x 10^6 Msun in the area we mapped and less than 10^7 Msun in the whole galaxy. This corresponds to a NH2/ICO ~ 4 x 10^{21} cm^-2 /(Kkm/s) over large scales, such as would be observed in distant objects, and half that in individual GMCs. No evidence was found for H2 without CO emission. Our simulations of the radiative transfer in clouds are entirely compatible with these NH2/ICO values. The SFE implied is a factor 5 - 10 higher than what is observed in large local universe spirals.Comment: 16 pages, 13 figures. Accepted for publication in Astronomy and Astrophysic

Dense Molecular Gas Associated with the Circumnuclear Star Forming Ring in the Barred Spiral Galaxy NGC 6951

We present high resolution (3" - 5") observations of CO(1-0) and HCN(1-0) emission from the circumnuclear star forming ring in the barred spiral galaxy NGC 6951, a host of a type-2 Seyfert, using the Nobeyama Millimeter Array and 45 m telescope. We find that most of the HCN emission is associated with the circumnuclear ring, where vigorous star formation occurs. The HCN to CO integrated intensity ratio is also enhanced in the star forming ring; the peak value of HCN/CO ratio is 0.18, which is comparable to the ratio in the starbursts NGC 253 and M82. The formation mechanism of dense molecular gas has been investigated. We find that the shocks along the orbit crowding do not promote the formation of the dense molecular gas effectively but enhance the presence of low density GMCs. Instead, gravitational instabilities of the gas can account for the dense molecular gas formation. The HCN/CO ratio toward the Seyfert nucleus of NGC 6951 is a rather normal value (0.086), in contrast with other Seyferts NGC 1068 and M51 where extremely high HCN/CO value of ~ 0.5 have been reported.Comment: 33 pages, 17 figures, to appear in the Astrophysical Journa

Particularly Efficient Star Formation in M33

The Star Formation (SF) rate in galaxies is an important parameter at all redshifts and evolutionary stages of galaxies. In order to understand the increased SF rates in intermediate redshift galaxies one possibility is to study star formation in local galaxies with properties frequently found at this earlier epoch like low metallicity and small size. We present sensitive observations of the molecular gas in M 33, a small Local Group spiral at a distance of 840 kpc which shares many of the characteristics of the intermediate redshift galaxies. The observations were carried out in the CO(2--1) line with the HERA heterodyne array on the IRAM 30 m telescope. A 11\arcmin$\times$22\arcmin region in the northern part of M 33 was observed, reaching a detection threshold of a few 10$^{3}$ \msol. The correlation in this field between the CO emission and tracers of SF (8\mum, 24\mum, \Ha, FUV) is excellent and CO is detected very far North, showing that molecular gas forms far out in the disk even in a small spiral with a subsolar metallicity. One major molecular cloud was discovered in an interarm region with no HI peak and little if any signs of SF -- without a complete survey this cloud would never have been found. The radial dependence of the CO emission has a scale length similar to the dust emission, less extended than the \Ha or FUV. If, however, the \ratioo ratio varies inversely with metallicity, then the scale length of the H$_2$ becomes similar to that of the \Ha or FUV. Comparing the SF rate to the H$_2$ mass shows that M 33, like the intermediate redshift galaxies it resembles, has a significantly higher SF efficiency than large local universe spirals.Comment: 16 pages, 15 figure