Black hole scaling relations of active and quiescent galaxies: Addressing selection effects and constraining virial factors

Local samples of quiescent galaxies with dynamically measured black hole masses (Mbh) may suffer from an angular resolution-related selection effect, which could bias the observed scaling relations between Mbh and host galaxy properties away from the intrinsic relations. In particular, previous work has shown that the observed Mbh-Mstar (stellar mass) relation is more strongly biased than the Mbh-sigma (velocity dispersion) relation. Local samples of active galactic nuclei (AGN) do not suffer from this selection effect, as in these samples Mbh is estimated from megamasers and/or reverberation mapping-based techniques. With the exception of megamasers, Mbh-estimates in these AGN samples are proportional to a virial coefficient fvir. Direct modelling of the broad line region suggests that fvir~3.5. However, this results in a Mbh-Mstar relation for AGN which lies below and is steeper than the one observed for quiescent black hole samples. A similar though milder trend is seen for the Mbh-sigma relation. Matching the high-mass end of the Mbh-Mstar and Mbh-sigma relations observed in quiescent samples requires fvir~15 and fvir~7, respectively. On the other hand, fvir~3.5 yields Mbh-sigma and Mbh-Mstar relations for AGN which are remarkably consistent with the expected `intrinsic' correlations for quiescent samples (i.e., once account has been made of the angular resolution-related selection effect), providing additional evidence that the sample of local quiescent black holes is biased. We also show that, as is the case for quiescent black holes, the Mbh-Mstar scaling relation of AGN is driven by velocity dispersion, thus providing additional key constraints to black hole-galaxy co-evolution models.Comment: 15 pages, 5 Figures. MNRAS, accepte

Yeast oxidosqualene cyclase (Erg7p) is a major component of lipid particles.

Oxidosqualene cyclase of the yeast encoded by the ERG7 gene converts oxidosqualene to lanosterol, the first cyclic component of sterol biosynthesis. In a previous study (Athenstaedt, K., Zweytick, D., Jandrositz, A, Kohlwein, S. D., and Daum, G. (1999) J. Bacteriol. 181, 6441–6448), Erg7p was identified as a component of yeast lipid particles. Here, we present evidence that Erg7p is almost exclusively associated with this compartment as shown by analysis of enzymatic activity, Western blot analysis, and in vivo localization of Erg7p-GFP. Occurrence of oxidosqualene cyclase in other organelles including the endoplasmic reticulum is negligible. In an erg7 deletion strain or in wild-type cells treated with an inhibitor of oxidosqualene cyclase, the substrate of Erg7p, oxidosqualene, accumulated mostly in lipid particles. Storage in lipid particles of this intermediate produced in excess may provide a possibility to exclude this membrane-perturbing component from other organelles. Thus, our data provide evidence that lipid particles are not only a depot for neutral lipids, but also participate in coordinate sterol metabolism and trafficking and serve as a storage site for compounds that may negatively affect membrane integrity

The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to impair tumour angiogenesis and metastasis dissemination

Aberrant cholesterol homeostasis and biosynthesis has been observed in different tumour types. This paper investigates the role of the post-squalenic enzyme of cholesterol biosynthesis, oxidosqualene cyclase (OSC), in regulating tumour angiogenesis and metastasis dissemination in mouse models of cancer. We showed that Ro 48-8071, a selective inhibitor of OSC, reduced vascular density and increased pericyte coverage, with a consequent inhibition of tumour growth in a spontaneous mouse model of pancreatic tumour (RIP-Tag2) and two metastatic mouse models of human colon carcinoma (HCT116) and pancreatic adenocarcinoma (HPAF-II). Remarkably, the inhibition of OSC hampered metastasis formation in HCT116 and HPAF-II models. Ro 48-8071 induced tumour vessel normalization and enhanced the anti-tumoral and anti-metastatic effects of 5-fluorouracil (5-FU) in HCT116 mice. Ro 48-8071 exerted a strong anti-angiogenic activity by impairing endothelial cell adhesion and migration, and by blocking vessel formation in angiogenesis assays. OSC inhibition specifically interfered with the PI3K pathway. According to in vitro results, Ro 48-8071 specifically inhibited Akt phosphorylation in both cancer cells and tumour vasculature in all treated models. Thus, our results unveil a crucial role of OSC in the regulation of cancer progression and tumour angiogenesis, and indicate Ro 48-8071 as a potential novel anti-angiogenic and anti-metastatic drug

The Many Manifestations of Downsizing: Hierarchical Galaxy Formation Models confront Observations

[abridged] It has been widely claimed that several lines of observational evidence point towards a "downsizing" (DS) of the process of galaxy formation over cosmic time. This behavior is sometimes termed "anti-hierarchical", and contrasted with the "bottom-up" assembly of the dark matter structures in Cold Dark Matter models. In this paper we address three different kinds of observational evidence that have been described as DS: the stellar mass assembly, star formation rate and the ages of the stellar populations in local galaxies. We compare a broad compilation of available data-sets with the predictions of three different semi-analytic models of galaxy formation within the Lambda-CDM framework. In the data, we see only weak evidence at best of DS in stellar mass and in star formation rate. We find that, when observational errors on stellar mass and SFR are taken into account, the models acceptably reproduce the evolution of massive galaxies, over the entire redshift range that we consider. However, lower mass galaxies are formed too early in the models and are too passive at late times. Thus, the models do not correctly reproduce the DS trend in stellar mass or the archaeological DS, while they qualitatively reproduce the mass-dependent evolution of the SFR. We demonstrate that these discrepancies are not solely due to a poor treatment of satellite galaxies but are mainly connected to the excessively efficient formation of central galaxies in high-redshift haloes with circular velocities ~100-200 km/s. [abridged]Comment: MNRAS accepted, 16 pages, 10 figure

Association between Thymic Function and Allogeneic Hematopoietic Stem Cell Transplantation Outcome: Results of a Pediatric Study

Abstract Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities