Evidence of strong quasar feedback in the early Universe

Most theoretical models invoke quasar driven outflows to quench star formation in massive galaxies, this feedback mechanism is required to account for the population of old and passive galaxies observed in the local universe. The discovery of massive, old and passive galaxies at z=2, implies that such quasar feedback onto the host galaxy must have been at work very early on, close to the reionization epoch. We have observed the [CII]158um transition in SDSSJ114816.64+525150.3 that, at z=6.4189, is one of the most distant quasars known. We detect broad wings of the line tracing a quasar-driven massive outflow. This is the most distant massive outflow ever detected and is likely tracing the long sought quasar feedback, already at work in the early Universe. The outflow is marginally resolved on scales of about 16 kpc, implying that the outflow can really affect the whole galaxy, as required by quasar feedback models. The inferred outflow rate, dM/dt > 3500 Msun/yr, is the highest ever found. At this rate the outflow can clean the gas in the host galaxy, and therefore quench star formation, in a few million years.Comment: 5 pages, 3 figures, accepted for publication in MNRAS Letter

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study

Summary: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year.Introduction: Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure.Methods: We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95 % confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91–180), past (181–364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out.Results: In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95 % CI = 1.46–2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95 % CI, 1.59–2.43).Conclusion: In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year

The physics and the structure of the quasar-driven outflow in Mrk 231

Massive AGN-driven outflows are invoked by AGN-galaxy co-evolutionary models to suppress both star formation and black hole accretion. Massive molecular outflows have recently been revealed in some AGN hosts. However, the physical properties and structure of these AGN-driven molecular outflows are still poorly constrained. Here we present new IRAM PdBI observations of Mrk231, the closest quasar known, targeting both the CO(1-0) and CO(2-1) transitions. We detect broad wings in both transitions, tracing a massive molecular outflow with velocities up to 800 km/s. The wings are spatially resolved at high significance level (5-11 sigma), indicating that the molecular outflow extends on the kpc scale. The CO(2-1)/CO(1-0) ratio of the red broad wings is consistent with the ratio observed in the narrow core, while the blue broad wing is less excited than the core. The latter result suggests that quasar driven outflow models invoking shocks (which would predict higher gas excitation) are not appropriate to describe the bulk of the outflow in Mrk231. However, we note that within the central 700 pc the CO(2-1)/CO(1-0) ratio of the red wing is slightly, but significantly, higher than in the line core, suggesting that shocks may play a role in the central region. We also find that the average size of the outflow anticorrelates with the critical density of the transition used as a wind tracer. This indicates that, although diffuse and dense clumps coexist in the outflowing gas, dense outflowing clouds have shorter lifetime and that they evaporate into the diffuse component along the outflow or, more simply, that diffuse clouds are more efficiently accelerated to larger distances by radiation pressure.Comment: 8 pages, 6 figures, accepted for publication in Astronomy and Astrophysic

Einstein, Planck and Vera Rubin: Relevant Encounters Between the Cosmological and the Quantum Worlds

In Cosmology and in Fundamental Physics there is a crucial question like: where the elusive substance that we call Dark Matter is hidden in the Universe and what is it made of? that, even after 40&nbsp;years from the Vera Rubin seminal discovery [1] does not have a proper answer. Actually, the more we have investigated, the more this issue has become strongly entangled with aspects that go beyond the established Quantum Physics, the Standard Model of Elementary particles and the General Relativity and related to processes like the Inflation, the accelerated expansion of the Universe and High Energy Phenomena around compact objects. Even Quantum Gravity and very exotic Dark Matter particle candidates may play a role in framing the Dark Matter mystery that seems to be accomplice of new unknown Physics. Observations and experiments have clearly indicated that the above phenomenon cannot be considered as already theoretically framed, as hoped for decades. The Special Topic to which this review belongs wants to penetrate this newly realized mystery from different angles, including that of a contamination of different fields of Physics apparently unrelated. We show with the works of this ST that this contamination is able to guide us into the required new Physics. This review wants to provide a good number of these \u201cpaths or contamination\u201d beyond/among the three worlds above; in most of the cases, the results presented here open a direct link with the multi-scale dark matter phenomenon, enlightening some of its important aspects. Also in the remaining cases, possible interesting contacts emerges. Finally, a very complete and accurate bibliography is provided to help the reader in navigating all these issues

Black hole accretion and host galaxies of obscured quasars in XMM-COSMOS

We explore the connection between black hole growth at the center of obscured quasars selected from the XMM-COSMOS survey and the physical properties of their host galaxies. We study a bolometric regime ( 8 x 10^45 erg/s) where several theoretical models invoke major galaxy mergers as the main fueling channel for black hole accretion. We confirm that obscured quasars mainly reside in massive galaxies (Mstar>10^10 Msun) and that the fraction of galaxies hosting such powerful quasars monotonically increases with the stellar mass. We stress the limitation of the use of rest-frame color-magnitude diagrams as a diagnostic tool for studying galaxy evolution and inferring the influence that AGN activity can have on such a process. We instead use the correlation between star-formation rate and stellar mass found for star-forming galaxies to discuss the physical properties of the hosts. We find that at z ~1, ~62% of Type-2 QSOs hosts are actively forming stars and that their rates are comparable to those measured for normal star-forming galaxies. The fraction of star-forming hosts increases with redshift: ~71% at z ~2, and 100% at z ~3. We also find that the the evolution from z ~1 to z ~3 of the specific star-formation rate of the Type-2 QSO hosts is in excellent agreement with that measured for star-forming galaxies. From the morphological analysis, we conclude that most of the objects are bulge-dominated galaxies, and that only a few of them exhibit signs of recent mergers or disks. Finally, bulge-dominated galaxies tend to host Type-2 QSOs with low Eddington ratios (lambda<0.1), while disk-dominated or merging galaxies have at their centers BHs accreting at high Eddington ratios (lambda > 0.1).Comment: Accepted by A&A. 20 pages, 16 figures, 2 tables. A version with higher resolution figures and SED fits of Appendix A is available at http://www.eso.org/~vmainier/QSO2/qso2.pd

Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion

Background: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. Methods: Adult Wistar rats underwent BCCAO/R with 30 min hypoperfusion followed by 60 min reperfusion. The frontal and temporal-occipital cortices and plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to determine concentrations of endocannabinoids (eCBs) and related molecules behaving as ligands of PPAR-alpha, and of oxidative-stress markers such as lipoperoxides, while Western Blot and immunohistochemistry were used to study protein expression of cannabinoid receptors, COX-2 and PPAR-alpha. Unpaired Student's t-test was used to evaluate statistical differences between groups. Results: The acute BCCAO/R procedure is followed by increased brain tissue levels of the eCBs 2-arachidonoylglycerol and anandamide, palmitoylethanolamide, an avid ligand of PPAR-alpha, lipoperoxides, type 1 (CB1) and type 2 (CB2) cannabinoid receptors, and COX-2, and decreased brain tissue concentrations of docosahexaenoic acid (DHA), one of the major targets of lipid peroxidation. In plasma, increased levels of anandamide and lipoperoxides were observed. Conclusions: The BCCAO/R stimulated early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The observed variations suggest that the positive modulation of the ECS and the increase of proinflammatory substances are directly correlated events. Increase of plasmatic levels of anandamide and lipoperoxides further suggests that dysregulation of these molecules may be taken as an indicator of an ongoing hypoperfusion/reperfusion challenge

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS