Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2

The Ras oncogene products regulate the expression of genes in transformed cells, and members of the Ets family of transcription factors have been implicated in this process. To determine which Ets factors are the targets of Ras signaling pathways, the abilities of several Ets factors to activate Ras-responsive enhancer (RRE) reporters in the presence of oncogenic Ras were examined. In transient transfection assay, reporters containing RREs composed of Ets-AP-1 binding sites could be activated 30-fold in NIH 3T3 fibroblasts and 80-fold in the macrophage-like line RAW264 by the combination of Ets1 or Ets2 and Ras but not by several other Ets factors that were tested in the assay. Ets2 and Ras also superactivated an RRE composed of Ets-Ets binding sites, but the Ets-responsive promoter of the c-fms gene was not superactivated. Mutation of a threonine residue to alanine in the conserved amino-terminal regions of Ets1 and Ets2 (threonine 38 and threonine 72, respectively) abrogated the ability of each of these proteins to superactivate reporter gene expression. Phosphoamino acid analysis of radiolabeled Ets2 revealed that Ras induced normally absent threonine-specific phosphorylation of the protein. The Ras-dependent increase in threonine phosphorylation was not observed in Ets2 proteins that had the conserved threonine 72 residue mutated to alanine or serine. These data indicate that Ets1 and Ets2 are specific nuclear targets of Ras signaling events and that phosphorylation of a conserved threonine residue is a necessary molecular component of Ras-mediated activation of these transcription factors

Maximum Likelihood Estimation in Gaussian Chain Graph Models under the Alternative Markov Property

The AMP Markov property is a recently proposed alternative Markov property for chain graphs. In the case of continuous variables with a joint multivariate Gaussian distribution, it is the AMP rather than the earlier introduced LWF Markov property that is coherent with data-generation by natural block-recursive regressions. In this paper, we show that maximum likelihood estimates in Gaussian AMP chain graph models can be obtained by combining generalized least squares and iterative proportional fitting to an iterative algorithm. In an appendix, we give useful convergence results for iterative partial maximization algorithms that apply in particular to the described algorithm.Comment: 15 pages, article will appear in Scandinavian Journal of Statistic

Signatures of the disk-jet coupling in the Broad-line Radio Quasar 4C+74.26

Here we explore the disk-jet connection in the broad-line radio quasar 4C+74.26, utilizing the results of the multiwavelength monitoring of the source. The target is unique in that its radiative output at radio wavelengths is dominated by a moderately-beamed nuclear jet, at optical frequencies by the accretion disk, and in the hard X-ray range by the disk corona. Our analysis reveals a correlation (local and global significance of 96\% and 98\%, respectively) between the optical and radio bands, with the disk lagging behind the jet by $250 \pm 42$ days. We discuss the possible explanation for this, speculating that the observed disk and the jet flux changes are generated by magnetic fluctuations originating within the innermost parts of a truncated disk, and that the lag is related to a delayed radiative response of the disk when compared with the propagation timescale of magnetic perturbations along relativistic outflow. This scenario is supported by the re-analysis of the NuSTAR data, modelled in terms of a relativistic reflection from the disk illuminated by the coronal emission, which returns the inner disk radius $R_{\rm in}/R_{\rm ISCO} =35^{+40}_{-16}$. We discuss the global energetics in the system, arguing that while the accretion proceeds at the Eddington rate, with the accretion-related bolometric luminosity $L_{\rm bol} \sim 9 \times 10^{46}$ erg s$^{-1}$ $\sim 0.2 L_{\rm Edd}$, the jet total kinetic energy $L_\textrm{j} \sim 4 \times 10^{44}$ erg s$^{-1}$, inferred from the dynamical modelling of the giant radio lobes in the source, constitutes only a small fraction of the available accretion power.Comment: 9 pages and 6 figures, ApJ accepte

High Energy gamma-rays From FR I Jets

Thanks to Hubble and Chandra telescopes, some of the large scale jets in extragalactic radio sources are now being observed at optical and X-ray frequencies. For the FR I objects the synchrotron nature of this emission is surely established, although a lot of uncertainties - connected for example with the particle acceleration processes involved - remain. In this paper we study production of high energy gamma-rays in FR I kiloparsec-scale jets by inverse-Compton emission of the synchrotron-emitting electrons. We consider different origin of seed photons contributing to the inverse-Compton scattering, including nuclear jet radiation as well as ambient, stellar and circumstellar emission of the host galaxies. We discuss how future detections or non-detections of the evaluated gamma-ray fluxes can provide constraints on the unknown large scale jet parameters, i.e. the magnetic field intensity and the jet Doppler factor. For the nearby sources Centaurus A and M 87, we find measurable fluxes of TeV photons resulting from synchrotron self-Compton process and from comptonisation of the galactic photon fields, respectively. In the case of Centaurus A, we also find a relatively strong emission component due to comptonisation of the nuclear blazar photons, which could be easily observed by GLAST at energy ~10 GeV, providing important test for the unification of FR I sources with BL Lac objects.Comment: 39 pages, 6 figures included. Modified version, accepted for publication in Astrophysical Journa

Rapid X-ray Declines and Plateaus in Swift GRB Light Curves Explained by A Highly Radiative Blast Wave

GRB X-ray light curves display rapid declines followed by a gradual steepening or plateau phase in >~ 30% of GRBs in the Swift sample. Treating the standard relativistic blastwave model in a uniform circumburst medium, it is shown that if GRBs accelerate ultra-high energy cosmic rays through a Fermi mechanism, then the hadronic component can be rapidly depleted by means of photopion processes on time scales ~100 - 10^4 s after the GRB explosion. While discharging the hadronic energy in the form of ultra-high energy cosmic ray neutrals and escaping cosmic-ray ions, the blast wave goes through a strongly radiative phase, causing the steep declines observed with Swift. Following the discharge, the blast wave recovers its adiabatic behavior, forming the observed plateaus or slow declines. These effects are illustrated by calculations of model bolometric light curves. The results show that steep X-ray declines and plateau features occur when GRB sources take place in rather dense media, with n >~ 100 cc out to >~ 10^17 cm.Comment: 13 pages, 7 figs, minor changes from previous version; accepted for publication in Ap

Radiation from the Relativistic Jet: a Role of the Shear Boundary Layer

Recent radio and optical large scale jets' observations suggest a two-component jet morphology, consisting of a fast central spine surrounded with a boundary layer with a velocity shear. We study radiation of electrons accelerated at such boundary layers as an option for standard approaches involving internal shocks in jets. The acceleration process in the boundary layer yields in a natural way a two component electron distribution: a power-law continuum with a bump at the energy, where energy gains equal radiation losses, followed by a cut-off. For such distributions we derive the observed spectra of synchrotron and inverse-Compton radiation, including comptonization of synchrotron and CMB photons. Under simple assumptions of energy equipartition between the relativistic particles and the magnetic field, the relativistic jet velocity at large scales and a turbulent character of the shear layer, the considered radiation can substantially contribute to the jet radiative output. In the considered conditions the synchrotron emission is characterized by a spectral index of the radio-to-optical continuum being approximately constant along the jet. A characteristic feature of the obtained broad-band synchrotron spectrum is an excess at X-ray frequencies, similar to the one observed in some objects by Chandra. As compared to the uniform jet models, the velocity shear across the radiating boundary region leads to decrease and frequency dependence of the observed jet-counterjet radio brightness asymmetry. We conclude that a careful investigation of the observational data looking for the derived effects can allow to evaluate the role of the boundary layer acceleration processes and/or impose constraints for the physical parameters of such layers in large scale jets.Comment: 30 pages, 4 figures included. Modified version, accepted for publication in Astrophysical Journa

Intracerebroventricular Ghrelin Administration Increases Depressive-Like Behavior in Male Juvenile Rats

Major depressive disorder (MDD) is arguably the largest contributor to the global disease and disability burden, but very few treatment options exist for juvenile MDD patients. Ghrelin is the principal hunger-stimulating peptide, and it has also been shown to reduce depressive-like symptoms in adult rodents. We examined the effects of intracerebroventricular (icv) injection of ghrelin on depressive-like behavior. Moreover, we determined whether ghrelin increased neurogenesis in the hippocampus. Ghrelin (0.2-nM, 0.5-nM, and 1.0-nM) was administered acutely by icv injection to juvenile rats to determine the most effective dose (0.5-nM) by a validated feeding behavior test and using the forced swim test (FST) as an indicator of depressive-like behavior. 0.5-nM ghrelin was then administered icv against an artificial cerebrospinal fluid (aCSF) vehicle control to determine behavioral changes in the tail suspension test (TST) as an indicator of depressive-like behavior. Neurogenesis was investigated using a mitogenic paradigm, as well as a neurogenic paradigm to assess whether ghrelin altered neurogenesis. Newborn hippocampal cells were marked using 5′-bromo-2′-deoxyuridine (BrdU) administered intraperitoneally (ip) at either the end or the beginning of the experiment for the mitogenic and neurogenic paradigms, respectively. We found that ghrelin administration increased immobility time in the TST. Treatment with ghrelin did not change mitogenesis or neurogenesis. These results suggest that ghrelin administration does not have an antidepressant effect in juvenile rats. In contrast to adult rodents, ghrelin increases depressive-like behavior in male juvenile rats. These results highlight the need to better delineate differences in the neuropharmacology of depressive-like behavior between juvenile and adult rodents

Multifrequency Photo-polarimetric WEBT Observation Campaign on the Blazar S5 0716+714: Source Microvariability and Search for Characteristic Timescales

Here we report on the results of the WEBT photo-polarimetric campaign targeting the blazar S5~0716+71, organized in March 2014 to monitor the source simultaneously in BVRI and near IR filters. The campaign resulted in an unprecedented dataset spanning $\sim 110$\,h of nearly continuous, multi-band observations, including two sets of densely sampled polarimetric data mainly in R filter. During the campaign, the source displayed pronounced variability with peak-to-peak variations of about $30\%$ and "bluer-when-brighter" spectral evolution, consisting of a day-timescale modulation with superimposed hourlong microflares characterized by $\sim 0.1$\,mag flux changes. We performed an in-depth search for quasi-periodicities in the source light curve; hints for the presence of oscillations on timescales of $\sim 3$\,h and $\sim 5$\,h do not represent highly significant departures from a pure red-noise power spectrum. We observed that, at a certain configuration of the optical polarization angle relative to the positional angle of the innermost radio jet in the source, changes in the polarization degree led the total flux variability by about 2\,h; meanwhile, when the relative configuration of the polarization and jet angles altered, no such lag could be noted. The microflaring events, when analyzed as separate pulse emission components, were found to be characterized by a very high polarization degree ($> 30\%$) and polarization angles which differed substantially from the polarization angle of the underlying background component, or from the radio jet positional angle. We discuss the results in the general context of blazar emission and energy dissipation models.Comment: 16 pages, 17 Figures; ApJ accepte