High resolution spectroscopy of the extended narrow-line region of IC 5063 and NGC 7212

We studied the properties of the gas of the extended narrow line region (ENLR) of two Seyfert 2 galaxies: IC 5063 and NGC 7212. We analysed high resolution spectra to investigate how the main properties of this region depend on the gas velocity. We divided the emission lines in velocity bins and we calculated several line ratios. Diagnostic diagrams and SUMA composite models (photo-ionization + shocks), show that in both galaxies there might be evidence of shocks significantly contributing in the gas ionization at high |V|, even though photo-ionization from the active nucleus remains the main ionization mechanism. In IC 5063 the ionization parameter depends on V and its trend might be explained assuming an hollow bi-conical shape for the ENLR, with one of the edges aligned with the galaxy disk. On the other hand, NGC 7212 does not show any kind of dependence. The models show that solar O/H relative abundances reproduce the observed spectra in all the analysed regions. They also revealed an high fragmentation of the gas clouds, suggesting that the complex kinematics observed in these two objects might be caused by interaction between the ISM and high velocity components, such as jets.Comment: 29 pages, 32 figures, accepted for publication in MNRA

Exploring the parent population of beamed NLS1s: from the black hole to the jet

The aim of this work is to understand the nature of the parent population of beamed narrow-line Seyfert 1 galaxies (NLS1s), by studying the physical properties of three parent candidates samples: steep-spectrum radio-loud NLS1s, radio-quiet NLS1s and disk-hosted radio-galaxies. In particular, we focused on the black hole mass and Eddington ratio distribution and on the interactions between the jet and the narrow-line region.Comment: 6 pages, 2 figures, to appear in Proceedings of High Energy Phenomena in Relativistic Outflows (HEPRO) V, Workshop Series of the Argentinian Astronomical Societ

Unveiling the parent population of beamed narrow-line Seyfert 1s

Narrow-line Seyfert 1 galaxies (NLS1s) are active galactic nuclei (AGN) recently identified as a new class of $\gamma$-ray sources. The high energy emission is explained by the presence of a relativistic jet observed at small angles, just like in the case of blazars. When the latter are observed at larger angles they appear as radio-galaxies, but an analogue parent population for beamed NLS1s has not yet been determined. In this work we analyze this problem by studying the physical properties of three different samples of parent sources candidates: steep-spectrum radio-loud NLS1s, radio-quiet NLS1s, and disk-hosted radio-galaxies, along with compact steep-spectrum sources. In our approach, we first derived black hole mass and Eddington ratio from the optical spectra, then we investigated the interaction between the jet and the narrow-line region from the [O III] $\lambda\lambda$4959,5007 lines. Finally, the radio luminosity function allowed us to compare their jet luminosity and hence determine the relations between the samples.Comment: 6 pages, no figures. Proceedings of the 28th Texas Symposium, Geneva, December 13-18, 201

po 032 displacement of hexokinase 2 from mitochondria induces mitochondrial ca2 overload and caspase independent cell death in cancer cells

Introduction Hexokinase 2 (HK2) phosphorylates glucose for starting its utilisation in glycolysis and pentose phosphate pathway. In many cancer cell types these processes are enhanced and HK2 expression is strongly induced and mainly localised to the outer mitochondrial membrane, where it also exerts an anti-apoptotic activity. Genetic ablation in mouse highlights HK2 importance in tumour formation. Therefore, HK2 is a good target for antineoplastic strategies, but HK2 inhibitors can have important side effects as they affect glucose metabolism. Here we have developed an antineoplastic strategy based on HK2 detachment from mitochondria in order to induce tumour cell death without inhibiting hexokinase enzymatic activity. Material and methods Peptide design and synthesis; hexokinase enzymatic activity assays. Measurements of mitochondrial membrane potential, intracellular Ca2+ levels, cell death and in vitro and in vivo tumorigenic assays on human and mouse cancer cell models (CT26 colon cancer cells, 4 T1 breast cancer cells, HeLa cervix carcinoma cells and primary human B-CLL cells). Results and discussions We have observed that in cancer cells HK2 locates at contact sites between mitochondria and endoplasmic reticulum called MAMs (mitochondria-associated membranes). We could selectively detach HK2 from MAMs by using a peptide that does not perturb hexokinase enzymatic activity. This treatment rapidly induces opening of the Inositol-3-Phospate-Receptor and the ensuing Ca2+ transfer from endoplasmic reticulum to mitochondria. As a consequence, a Ca2+ overload occurs in mitochondria, leading to permeability transition pore opening, mitochondrial membrane depolarization and apoptosis in a caspase-independent way. Peptide administration reduces allografic growth of breast and colon cancer cells without any noxious effect on healthy tissues, and elicits death of B-cell chronic lymphocytic leukaemia (B-CLL) cells freshly obtained by patients and in vivo. Conclusion We have reported that HK2 locates in MAMs of cancer cells, where it acts as an important player in the control of their survival. Targeting HK2 with a peptide-based strategy constitutes a novel and promising anti-neoplastic approach

Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration

Splenic marginal zone lymphoma: a prognostic model for clinical use.

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100 000/μL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (x 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient. © 2006 by The American Society of Hematology

The Interacting Late-type Host Galaxy of the Radio-loud Narrow-line Seyfert 1 IRAS 20181-2244

Narrow-line Seyfert 1 galaxies (NLS1s) are a class of active galactic nuclei that are known to be one of the few sources of gamma-rays, which originate in a relativistic beamed jet. Because of their relatively large distance, a poorly investigated aspect of these jetted NLS1s is their environment, and in particular, their host galaxy. In this work, we present the results of a morphological analysis of the host galaxy of the jetted NLS1 IRAS 20181-2244 observed with the 6.5 m Baade Telescope of the Las Campanas Observatory. The GALFIT analysis run on the Ks image, along with additional spectroscopic observations performed with the Nordic Optical Telescope, clearly revealed the presence of an interacting system of two galaxies. The data suggest that this NLS1 is hosted by a late-type galaxy, although the result is not conclusive. This analysis, along with other results in the literature, might suggest that two populations of jetted NLS1 exist. Further morphological studies are needed to confirm or disprove this hypothesis

HS1, a Lyn Kinase Substrate, Is Abnormally Expressed in B-Chronic Lymphocytic Leukemia and Correlates with Response to Fludarabine-Based Regimen

In B-Chronic Lymphocytic Leukemia (B-CLL) kinase Lyn is overexpressed, active, abnormally distributed, and part of a cytosolic complex involving hematopoietic lineage cell-specific protein 1 (HS1). These aberrant properties of Lyn could partially explain leukemic cells’ defective apoptosis, directly or through its substrates, for example, HS1 that has been associated to apoptosis in different cell types. To verify the hypothesis of HS1 involvement in Lyn-mediated leukemic cell survival, we investigated HS1 protein in 71 untreated B-CLL patients and 26 healthy controls. We found HS1 overexpressed in leukemic as compared to normal B lymphocytes (1.38±0.54 vs 0.86±0.29, p<0.01), and when HS1 levels were correlated to clinical parameters we found a higher expression of HS1 in poor-prognosis patients. Moreover, HS1 levels significantly decreased in ex vivo leukemic cells of patients responding to a fludarabine-containing regimen. We also observed that HS1 is partially localized in the nucleus of neoplastic B cells. All these data add new information on HS1 study, hypothesizing a pivotal role of HS1 in Lyn-mediated modulation of leukemic cells’ survival and focusing, one more time, the attention on the BCR-Lyn axis as a putative target for new therapeutic strategies in this disorder

MD simulation of xenon in ionic liquids: Disentangling the cationic and anionic cage effects on the structural and dynamic properties

We present a computational and theoretical study of the microscopic structure of two representative ionic liquids as probed by using xenon. Trajectories obtained from classical molecular dynamics simulations of xenon dissolved in [bmim][Cl] and [bmim][PF6] have been used to define the cage of xenon following a theoretical modeling introduced some years ago for simple fluids. The separate contribution of cations and anions to the caging of xenon has been disentangled, showing a major contribution from the cations. Moreover the coupled dynamics of the probe and the associated cage have been analyzed. The distribution of librational frequencies for the putative motion of the probe within the cage of the two systems shows clear, though not large, differences. The diffusion coefficients of cations, anions and xenon support the validity of hydrodynamic theory