Compact Symmetric Objects -- I Towards a Comprehensive Bona Fide Catalog

Compact Symmetric Objects (CSOs) are jetted Active Galactic Nuclei (AGN) with overall projected size <1 kpc. The classification was introduced to distinguish these objects from the majority of compact jetted-AGN in centimeter wavelength very long baseline interferometry observations, where the observed emission is relativistically boosted towards the observer. The original classification criteria for CSOs were: (i) evidence of emission on both sides of the center of activity, and (ii) overall size <1 kpc. However some relativistically boosted objects with jet axes close to the line of sight appear symmetric and have been mis-classified as CSOs, thereby undermining the CSO classification. This is because two essential CSO properties, pointed out in the original papers, have been neglected: (iii) low variability, and (iv) low apparent speeds along the jets. As a first step towards creating a comprehensive catalog of ``bona fide'' CSOs, we identify 79 bona fide CSOs, including 15 objects claimed as confirmed CSOs here for the first time, that match the CSO selection criteria. This sample of bona fide CSOs can be used for astrophysical studies of CSOs without contamination by mis-classified CSOs. We show that the fraction of CSOs in complete flux density limited AGN samples with S$_{\rm 5\,GHz}$ >700 mJy is between $(6.8\pm1.6)$% and $(8.5\pm1.8)$%.Comment: 28 pages, 9 figures, 3 tables, accepted for publicatio

Compact Symmetric Objects -- II Confirmation of a Distinct Population of High-Luminosity Jetted Active Galaxies

Compact Symmetric Objects (CSOs) are compact (<1 kpc), jetted Active Galactic Nuclei (AGN), whose jet axes are not aligned close to the line of sight, and whose observed emission is not predominantly relativistically boosted towards us. Two classes of CSOs have previously been identified: approximately one fifth are edge-dimmed and designated as CSO 1s, while the rest are edge brightened and designated as CSO 2s. This paper focuses almost exclusively on CSO 2s. Using complete samples of CSO 2s we present three independent lines of evidence, based on their relative numbers, redshift distributions, and size distributions, which show conclusively that the vast majority (> 99%) of CSO 2s do not evolve into larger-scale radio sources. These CSO 2s belong to a distinct population of jetted-AGN, which should be characterized as ``short-lived'' compared to the classes of larger jetted-AGN, as opposed to ``young''. We show that there is a sharp upper cutoff in the CSO 2 size distribution at $\approx 500$ pc. The distinct differences between most CSO 2s and other jetted-AGN provides a crucial new time domain window on the formation and evolution of relativistic jets in AGN and the supermassive black holes that drive them.Comment: 29 pages, 10 figures, 7 tables, accepted for publicatio

Compact Symmetric Objects -- III Evolution of the High-Luminosity Branch and a Possible Connection with Tidal Disruption Events

We use a sample of 54 Compact Symmetric Objects (CSOs) to confirm that there are two unrelated CSO classes: an edge-dimmed, low-luminosity class (CSO~1), and an edge-brightened, high-luminosity class (CSO~2). Using blind tests, we show that CSO~2s consist of three sub-classes: CSO 2.0, having prominent hot-spots at the leading edges of narrow jets and/or narrow lobes; CSO~2.2, without prominent hot-spots, and with broad jets and/or lobes; and CSO~2.1, which exhibit mixed properties. Most CSO 2s do not evolve into larger jetted-AGN, but spend their whole life-cycle as CSOs of size $\lesssim$500 pc and age $\lesssim$5000 yr. The minimum energies needed to produce the radio luminosity and structure in CSO~2s range from $\sim~10^{-4}\,M_\odot{c}^2$ to $\sim7\,M_\odot{c}^2$. We show that the transient nature of most CSO~2s, and their birthrate, can be explained through ignition in the tidal disruption events of giant stars. We also consider possibilities of tapping the spin energy of the supermassive black hole, and tapping the energy of the accretion disk. Our results demonstrate that CSOs constitute a large family of AGN in which we have thus far studied only the brightest. More comprehensive CSO studies, with higher sensitivity, resolution, and dynamic range, will revolutionize our understanding of AGN and the central engines that power them.Comment: 44 pages, 16 figures, 9 tables, accepted for publicatio

High dynamic range JVLA observations of Perseus Cluster Radio Galaxies

Galaxie

Estrogen Receptor β-Selective Agonists Stimulate Calcium Oscillations in Human and Mouse Embryonic Stem Cell-Derived Neurons

Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER) in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERα and ERβ on calcium oscillations in neurons derived from human (hES) and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERβ, but not ERα. The non-selective ER agonist 17β-estradiol (E2) rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERα agonist 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT). In contrast, the selective ERβ agonists, 2,3-bis(4-Hydroxyphenyl)-propionitrile (DPN), MF101, and 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041) stimulated calcium oscillations similar to E2. The ERβ agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERβ activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERβ signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds

StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation

Recent studies have demonstrated that human stearoylCoA desaturase-1 (SCD1), a Δ9-desaturase that converts saturated fatty acids (SFA) into monounsaturated fatty acids, controls the rate of lipogenesis, cell proliferation and tumorigenic capacity in cancer cells. However, the biological function of stearoylCoA desaturase-5 (SCD5), a second isoform of human SCD that is highly expressed in brain, as well as its potential role in human disease, remains unknown. In this study we report that the constitutive overexpression of human SCD5 in mouse Neuro2a cells, a widely used cell model of neuronal growth and differentiation, displayed a greater n-7 MUFA-to-SFA ratio in cell lipids compared to empty-vector transfected cells (controls). De novo synthesis of phosphatidylcholine and cholesterolesters was increased whereas phosphatidylethanolamine and triacylglycerol formation was reduced in SCD5-expressing cells with respect to their controls, suggesting a differential use of SCD5 products for lipogenic reactions. We also observed that SCD5 expression markedly accelerated the rate of cell proliferation and suppressed the induction of neurite outgrowth, a typical marker of neuronal differentiation, by retinoic acid indicating that the desaturase plays a key role in the mechanisms of cell division and differentiation. Critical signal transduction pathways that are known to modulate these processes, such epidermal growth factor receptor (EGFR)Akt/ERK and Wnt, were affected by SCD5 expression. Epidermal growth factor-induced phosphorylation of EGFR, Akt and ERK was markedly blunted in SCD5-expressing cells. Furthermore, the activity of canonical Wnt was reduced whereas the non-canonical Wnt was increased by the presence of SCD5 activity. Finally, SCD5 expression increased the secretion of recombinant Wnt5a, a non-canonical Wnt, whereas it reduced the cellular and secreted levels of canonical Wnt7b. Our data suggest that, by a coordinated modulation of key lipogenic pathways and transduction signaling cascades, SCD5 participates in the regulation of neuronal cell growth and differentiation

The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways

Modulation of the β-Catenin Signaling Pathway by the Dishevelled-Associated Protein Hipk1

BACKGROUND:Wnts are evolutionarily conserved ligands that signal through beta-catenin-dependent and beta-catenin-independent pathways to regulate cell fate, proliferation, polarity, and movements during vertebrate development. Dishevelled (Dsh/Dvl) is a multi-domain scaffold protein required for virtually all known Wnt signaling activities, raising interest in the identification and functions of Dsh-associated proteins. METHODOLOGY:We conducted a yeast-2-hybrid screen using an N-terminal fragment of Dsh, resulting in isolation of the Xenopus laevis ortholog of Hipk1. Interaction between the Dsh and Hipk1 proteins was confirmed by co-immunoprecipitation assays and mass spectrometry, and further experiments suggest that Hipk1 also complexes with the transcription factor Tcf3. Supporting a nuclear function during X. laevis development, Myc-tagged Hipk1 localizes primarily to the nucleus in animal cap explants, and the endogenous transcript is strongly expressed during gastrula and neurula stages. Experimental manipulations of Hipk1 levels indicate that Hipk1 can repress Wnt/beta-catenin target gene activation, as demonstrated by beta-catenin reporter assays in human embryonic kidney cells and by indicators of dorsal specification in X. laevis embryos at the late blastula stage. In addition, a subset of Wnt-responsive genes subsequently requires Hipk1 for activation in the involuting mesoderm during gastrulation. Moreover, either over-expression or knock-down of Hipk1 leads to perturbed convergent extension cell movements involved in both gastrulation and neural tube closure. CONCLUSIONS:These results suggest that Hipk1 contributes in a complex fashion to Dsh-dependent signaling activities during early vertebrate development. This includes regulating the transcription of Wnt/beta-catenin target genes in the nucleus, possibly in both repressive and activating ways under changing developmental contexts. This regulation is required to modulate gene expression and cell movements that are essential for gastrulation