Compact radio sources:Triggering and feedback

CSS/GPS objects represent a key stage in the evolution of powerful radio AGN in which the jets are expanding through the denser, kpc-scale ISM in the host galaxies. Therefore, it is important both to understand how such radio AGN are triggered as galaxies evolve and to directly quantify the impact of the outflows induced by the jet-cloud interactions. Here, we show that CSS/GPS sources are likely to be triggered in galaxy mergers, just like powerful radio AGN in general. However, they are both more gas-rich and have higher star formation rates on average than their more extended counterparts. Also, whereas observations frequently show evidence for strong jet-cloud interactions in CSS/GPS in the form of warm outflows, in most cases these warm outflows are unlikely to be energetic enough to affect the star formation histories of the entire host galaxies outside the central kpc. Rather, much of the mass, energy, and momentum of the outflows appear to be tied up in neutral and molecular outflows, which may have a more important impact on the host galaxies. Finally, we consider whether CSS/GPS sources are impostors in flux-limited samples due to the effect of the strong jet-cloud interactions on their radio luminosities

Ionised gas outflows over the radio AGN life cycle

Feedback from AGN is known to affect the host galaxy's evolution. In radio AGN, one manifestation of feedback is seen in gas outflows. However, it is still not well understood whether the effect of feedback evolves with the radio AGN life cycle. In this study, we investigate this link using the radio spectral shape as a proxy for the evolutionary stage of the AGN. We used [OIII] emission line spectra to trace the presence of outflows on the ionised gas. Using a sample of uniformly selected 129 radio AGN with $L_\textrm{1.4GHz}\approx10^{23}-10^{26}$ W Hz$^{-1}$, and a mean stacking analysis of the [OIII] profile, we conclude that the ionised gas outflow is linked to the radio spectral shape, and it evolves with the evolution of the radio source. We find that sources with a peak in their radio spectra (optically thick), on average, drive a broad outflow ($FWHM\approx1330\pm418$ km s$^{-1}$) with a velocity $v_\textrm{out}\approx 240$ km s$^{-1}$. However, we detect no outflow in the stacked [OIII] profile of sources without a peak in their radio spectrum. In addition, we find that individual outflow detections are kinematically more extreme in peaked than non-peaked sources. We conclude that radio jets are most effective at driving gas outflows when young, and the outflow is typically short lived. Our stacking analysis shows no significant dependence of the presence of ionised gas outflows on the radio morphology, 1.4 GHz luminosity, optical luminosity and Eddington ratio of these sources. We also identify candidate restarted AGN in our sample, whose [OIII] profiles suggest that they have more disturbed gas kinematics than their evolved counterparts, although the evidence for this is tentative. Our findings support the picture where the impact of AGN feedback changes as the source evolves, and young radio jets interact with the ambient medium, clearing a channel of gas as they expand.Comment: 20 pages, 12 figures. Accepted for publication in Astronomy and Astrophysic

Introduction to Epigenetics

This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to diseas

Radio Jets as Driving Mechanism of Fast Outflows: The HI View

The complex and multi-phase nature of gas outflows is one of the properties highlighted by the work in recent years on AGN-driven outflows. In particular, the cold gas is found to play a more important role than previously expected. Surprisingly, HI has been shown to be a good tracer of fast outflows. In radio AGN, we can trace these outflows by looking at HI in absorption. I will present the results from a survey (done with the Westerbork Synthesis Radio Telescope) of radio sources up to z = 0.2, which has allowed us to explore, for the first time in a systematic way, the occurrence of HI outflows. A number of new cases have been found, showing outflow velocity up to about 1000 km/s. We have followed up some interesting cases with HI observations at high spatial resolution (reaching the pc scale with VLBI). In this way, we have located the region(s) where the HI outflows occur and investigated the role of the radio jets as driving mechanism. This relatively shallow survey was done in preparation of the upcoming "blind" surveys about to start with SKA pathfinders (Apertif, ASKAP, MeerKat). These surveys will allow two important steps forward: build up much better statistics of the HI outflows, and extend this search to higher redshifts to investigate whether any evolution is seen in their occurrence and properties. I will summarise the status of these projects

ARTD2 activity is stimulated by RNA

ADP-ribosyltransferases (ARTs) are important enzymes that regulate the genotoxic stress response and the maintenance of genome integrity. ARTD1 (PARP1) and ARTD2 (PARP2) are homologous proteins that modify themselves and target proteins by the addition of mono- and poly-ADP-ribose (PAR) moieties. Both enzymes have been described to be involved in the genotoxic stress response. Here, we characterize cellular PAR formation on hydrogen peroxide (H2O2) or N-methyl-N′-methyl-nitro-N-nitrosoguanidine (MNNG) stress, in combination with application of the RNA polymerase I inhibitor Actinomycin D (ActD), known to cause accumulation of short RNA polymerase I-dependent rRNA transcripts. Intriguingly, co-treatment with ActD substantially increased H2O2- or MNNG-induced PAR formation. In cells, this enhancement was predominantly mediated by ARTD2 and not ARTD1. In vitro experiments confirmed that ARTD2 is strongly activated by RNA and that the N-terminal SAP domain is important for the binding to RNA. Thus, our findings identify a new activator of ARTD2-dependent ADP-ribosylation, which has important implications for the future analysis of the biological role of ARTD2 in the nucleu

Nucleolus and rRNA gene chromatin in early embryo development

The nucleolus is the largest substructure in the nucleus and forms around the nucleolar organizer regions (NORs), which comprise hundreds of rRNA genes. Recent evidence highlights further functions of the nucleolus that go beyond ribosome biogenesis. Data indicate that the nucleolus acts as a compartment for the location and regulation of repressive genomic domains and, together with the nuclear lamina, represents the hub for the organization of the inactive heterochromatin. In this review, we discuss recent findings that have revealed how nucleolar structure and rRNA gene chromatin states are regulated during early mammalian development and their contribution to the higher-order spatial organization of the genome

Spleen histology in children with sickle cell disease and hereditary spherocytosis: Hints on the disease pathophysiology

open2Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histological and morphometric features of HS and SCD spleens, in order to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS and control patients the following parameters were considered: (i) macroscopic features; (ii) lymphoid follicle (LF) density; (iii) presence of peri-follicular marginal zones (MZs); (iv) presence of Gamna-Gandy bodies; (v) density of CD8-positive sinusoids; (vi) density of CD34-positive microvessels; (vii) presence/distribution of fibrosis and SMA-positive myoid cells; (viii) density of CD68-positive macrophages. SCD and HS spleens have similar macroscopic features. SCD spleens had lower LF density and fewer MZs than HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, the majority of HS spleens clustered with controls, while SCD grouped separately. A multi-parametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.embargoed_20161128Alaggio, RitaAlaggio, Rita; Gamba, Piergiorgi

Image analysis workflows to reveal the spatial organization of cell nuclei and chromosomes

Nucleus, chromatin, and chromosome organization studies heavily rely on fluorescence microscopy imaging to elucidate the distribution and abundance of structural and regulatory components. Three-dimensional (3D) image stacks are a source of quantitative data on signal intensity level and distribution and on the type and shape of distribution patterns in space. Their analysis can lead to novel insights that are otherwise missed in qualitative-only analyses. Quantitative image analysis requires specific software and workflows for image rendering, processing, segmentation, setting measurement points and reference frames and exporting target data before further numerical processing and plotting. These tasks often call for the development of customized computational scripts and require an expertise that is not broadly available to the community of experimental biologists. Yet, the increasing accessibility of high- and super-resolution imaging methods fuels the demand for user-friendly image analysis workflows. Here, we provide a compendium of strategies developed by participants of a training school from the COST action INDEPTH to analyze the spatial distribution of nuclear and chromosomal signals from 3D image stacks, acquired by diffraction-limited confocal microscopy and super-resolution microscopy methods (SIM and STED). While the examples make use of one specific commercial software package, the workflows can easily be adapted to concurrent commercial and open-source software. The aim is to encourage biologists lacking custom-script-based expertise to venture into quantitative image analysis and to better exploit the discovery potential of their images.Abbreviations: 3D FISH: three-dimensional fluorescence in situ hybridization; 3D: three-dimensional; ASY1: ASYNAPTIC 1; CC: chromocenters; CO: Crossover; DAPI: 4',6-diamidino-2-phenylindole; DMC1: DNA MEIOTIC RECOMBINASE 1; DSB: Double-Strand Break; FISH: fluorescence in situ hybridization; GFP: GREEN FLUORESCENT PROTEIN; HEI10: HUMAN ENHANCER OF INVASION 10; NCO: Non-Crossover; NE: Nuclear Envelope; Oligo-FISH: oligonucleotide fluorescence in situ hybridization; RNPII: RNA Polymerase II; SC: Synaptonemal Complex; SIM: structured illumination microscopy; ZMM (ZIP: MSH4: MSH5 and MER3 proteins); ZYP1: ZIPPER-LIKE PROTEIN 1

Differential Expression of Kisspeptin System and Kisspeptin Receptor Trafficking during Spermatozoa Transit in the Epididymis

The hypothalamus–pituitary–testis axis controls the production of spermatozoa, and the kisspeptin system, comprising Kiss1 and Kiss1 receptor (Kiss1R), is the main central gatekeeper. The activity of the kisspeptin system also occurs in testis and spermatozoa, but currently the need of peripheral kisspeptin to produce gametes is not fully understood. Hence, we characterized kisspeptin system in rat spermatozoa and epididymis caput and cauda and analyzed the possible presence of Kiss1 in the epididymal fluid. The presence of Kiss1 and Kiss1R in spermatozoa collected from epididymis caput and cauda was evaluated by Western blot; significant high Kiss1 levels in the caput (p < 0.001 vs. cauda) and constant levels of Kiss1R proteins were observed. Immunofluorescence analysis revealed that the localization of Kiss1R in sperm head shifts from the posterior region in the epididymis caput to perforatorium in the epididymis cauda. In spermatozoa-free epididymis, Western blot revealed higher expression of Kiss1 and Kiss1R in caput (p < 0.05 vs. cauda). Moreover, immunohistochemistry revealed that Kiss1 and Kiss1R proteins were mainly localized in the secretory epithelial cell types and in contractile myoid cells, respectively. Finally, both dot blot and Elisa revealed the presence of Kiss1 in the epididymal fluid collected from epididymis cauda and caput, indicating that rat epididymis and spermatozoa possess a complete kisspeptin system. In conclusion, we reported for the first time in rodents Kiss1R trafficking in spermatozoa during the epididymis transit and Kiss1 measure in the epididymal fluid, thus suggesting a possible role for the system in spermatozoa maturation and storage within the epididymis

PRAMEL7/CUL2 axis regulates NuRD stability to establish ground-state pluripotency in embryonic stem cells

Pluripotency is established in E4.5 preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of pluripotency, however, they only partially resemble the gene expression signature of developmental ground-state. Induced PRAMEL7 expression, a protein highly expressed in the ICM but lowly expressed in ESCs, reprograms developmentally advanced ESC+serum into ground-state pluripotency by causing DNA hypomethylation and gene expression signature close to developmental ground-state. However, how PRAMEL7 reprograms gene expression remains elusive. Here we show that PRAMEL7 associates with Cullin2 (CUL2) and this interaction is required to establish ground-state gene expression. PRAMEL7 recruits CUL2 to chromatin and targets for proteasomal degradation regulators of repressive chromatin, including NuRD complex. PRAMEL7 antagonizes NuRD-mediated repression of genes implicated in pluripotency by decreasing NuRD stability and promoter association in a CUL2-dependent manner. Our data link proteasome degradation pathways to ground-state gene expression, offering insights to generate in vitro models to reproduce the in vivo ground-state pluripotency