Evolution of Supermassive Black Holes from Cosmological Simulations

The correlations between the mass of supermassive black holes and properties of their host galaxies are investigated through cosmological simulations. Black holes grow from seeds of 100 solar masses inserted into density peaks present in the redshift range 12-15. Seeds grow essentially by accreting matter from a nuclear disk and also by coalescences resulting from merger episodes. At z=0, our simulations reproduce the black hole mass function and the correlations of the black hole mass both with stellar velocity dispersion and host dark halo mass. Moreover, the evolution of the black hole mass density derived from the present simulations agrees with that derived from the bolometric luminosity function of quasars, indicating that the average accretion history of seeds is adequately reproduced . However, our simulations are unable to form black holes with masses above $10^9 M_{\odot}$ at $z\sim 6$, whose existence is inferred from the bright quasars detected by the Sloan survey in this redshift range.Comment: Talk given at the International Workshop on Astronomy and Relativistic Astrophysics (IWARA 2009), Maresias, Brazil. to be published in the International Journal of Modern Physics

Coalescence Rate of Supermassive Black Hole Binaries Derived from Cosmological Simulations: Detection Rates for LISA and ET

The coalescence history of massive black holes has been derived from cosmological simulations, in which the evolution of those objects and that of the host galaxies are followed in a consistent way. The present study indicates that supermassive black holes having masses greater than $\sim 10^{9} M_{\odot}$ underwent up to 500 merger events along their history. The derived coalescence rate per comoving volume and per mass interval permitted to obtain an estimate of the expected detection rate distribution of gravitational wave signals ("ring-down") along frequencies accessible by the planned interferometers either in space (LISA) or in the ground (Einstein). For LISA, in its original configuration, a total detection rate of about $15 yr^{-1}$ is predicted for events having a signal-to-noise ratio equal to 10, expected to occur mainly in the frequency range $4-9 mHz$. For the Einstein gravitational wave telescope, one event each 14 months down to one event each 4 years is expected with a signal-to-noise ratio of 5, occurring mainly in the frequency interval $10-20 Hz$. The detection of these gravitational signals and their distribution in frequency would be in the future an important tool able to discriminate among different scenarios explaining the origin of supermassive black holes.Comment: 18 pages, 7 figures, to appear in the IJMP

Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5

Capture Rates of Compact Objects by Supermassive Black Holes

Capture rates of compact objects were calculated by using a recent solution of the Fokker-Planck equation in energy-space, including two-body resonant effects. The fraction of compact objects (white dwarfs, neutron stars and stellar black holes) was estimated as a function of the luminosity of the galaxy from a new grid of evolutionary models. Stellar mass densities at the influence radius of central supermassive black holes were derived from brightness profiles obtained by Hubble Space Telescope observations. The present study indicates that the capture rates scale as $\propto M_{bh}^{-1.048}$, consequence of the fact that dwarf galaxies have denser central regions than luminous objects. If the mass distribution of supermassive black holes has a lower cutoff at $\sim 1.4\times 10^6$ M$_{\odot}$ (corresponding to the lowest observed supermassive black hole mass, located in M32), then 9 inspiral events are expected to be seen by LISA (7-8 corresponding to white dwarf captures and 1-2 to neutron star and stellar black hole captures) after one year of operation. However, if the mass distribution extends down to $\sim 2\times 10^5$ M$_{\odot}$, then the total number of expected events increases up to 579 (corresponding to $\sim$ 274 stellar black hole captures, $\sim$ 194 neutron star captures and $\sim$ 111 white dwarf captures).Comment: 8 pages, 3 figures; accepted for publication in PR

A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome

A follow-up study of a large Utah family with significant linkage to chromosome 2q24 led us to identify a new febrile seizure (FS) gene, SCN9A encoding Na(v)1.7. In 21 affected members, we uncovered a potential mutation in a highly conserved amino acid, p.N641Y, in the large cytoplasmic loop between transmembrane domains I and II that was absent from 586 ethnically matched population control chromosomes. To establish a functional role for this mutation in seizure susceptibility, we introduced the orthologous mutation into the murine Scn9a ortholog using targeted homologous recombination. Compared to wild-type mice, homozygous Scn9a(N641Y/N641Y) knockin mice exhibit significantly reduced thresholds to electrically induced clonic and tonic-clonic seizures, and increased corneal kindling acquisition rates. Together, these data strongly support the SCN9A p.N641Y mutation as disease-causing in this family. To confirm the role of SCN9A in FS, we analyzed a collection of 92 unrelated FS patients and identified additional highly conserved Na(v)1.7 missense variants in 5% of the patients. After one of these children with FS later developed Dravet syndrome (severe myoclonic epilepsy of infancy), we sequenced the SCN1A gene, a gene known to be associated with Dravet syndrome, and identified a heterozygous frameshift mutation. Subsequent analysis of 109 Dravet syndrome patients yielded nine Na(v)1.7 missense variants (8% of the patients), all in highly conserved amino acids. Six of these Dravet syndrome patients with SCN9A missense variants also harbored either missense or splice site SCN1A mutations and three had no SCN1A mutations. This study provides evidence for a role of SCN9A in human epilepsies, both as a cause of FS and as a partner with SCN1A mutations

Gravitational torque-driven black hole growth and feedback in cosmological simulations

We investigate black hole-host galaxy scaling relations in cosmological simulations with a self-consistent black hole growth and feedback model. The sub-grid accretion model captures the key scalings governing angular momentum transport from galactic scales down to parsec scales, while our kinetic feedback implementation enables the injection of outflows with properties chosen to match observed nuclear outflows. We show that "quasar mode" feedback can have a large impact on the thermal properties of the intergalactic medium and the growth of galaxies and massive black holes for kinetic feedback efficiencies as low as 0.1% relative to the bolometric luminosity. Nonetheless, our simulations suggest that the black hole-host scaling relations are only weakly dependent on the effects of black hole feedback on galactic scales, owing to feedback suppressing the growth of galaxies and massive black holes by a similar amount. In contrast, the rate at which gravitational torques feed the central black hole relative to the host galaxy star formation rate governs the slope and normalization of the black hole-host correlations. Our results suggest that a common gas supply regulated by gravitational torques is the primary driver of the observed co-evolution of black holes and galaxies.Comment: 13 pages, 11 figures, submitted to MNRA

Chemical Analysis of Cellular and Extracellular Carbohydrates of a Biofilm-Forming Strain Pseudomonas aeruginosa PA14

Background: Pseudomonas aeruginosa is a Gram-negative bacterium and an opportunistic pathogen, which causes persisting life-threatening infections in cystic fibrosis (CF) patients. Biofilm mode of growth facilitates its survival in a variety of environments. Most P. aeruginosa isolates, including the non-mucoid laboratory strain PA14, are able to form a thick pellicle, which results in a surface-associated biofilm at the air-liquid (A\ufffdL) interface in standing liquid cultures. Exopolysaccharides (EPS) are considered as key components in the formation of this biofilm pellicle. In the non-mucoid P. aeruginosa strain PA14, the \ufffd\ufffdscaffolding\ufffd\ufffd polysaccharides of the biofilm matrix, and the molecules responsible for the structural integrity of rigid A\ufffdL biofilm have not been identified. Moreover, the role of LPS in this process is unclear, and the chemical structure of the LPS O-antigen of PA14 has not yet been elucidated. Principal Findings: In the present work we carried out a systematic analysis of cellular and extracellular (EC) carbohydrates of P. aeruginosa PA14. We also elucidated the chemical structure of the LPS O-antigen by chemical methods and 2-D NMR spectroscopy. Our results showed that it is composed of linear trisaccharide repeating units, identical to those described for P. aeruginosa Lanyi type O:2a,c (Lanyi-Bergman O-serogroup 10a, 10c; IATS serotype 19) and having the following structure: -4)-a-L-GalNAcA-(1\ufffd3)-a-D-QuiNAc-(1\ufffd3)- a-L-Rha-(1-. Furthermore, an EC O-antigen polysaccharide (EC O-PS) and the glycerol-phosphorylated cyclic b-(1,3)-glucans were identified in the culture supernatant of PA14, grown statically in minimal medium. Finally, the extracellular matrix of the thick biofilm formed at the A-L interface contained, in addition to eDNA, important quantities (at least ,20% of dry weight) of LPS-like material. Conclusions: We characterized the chemical structure of the LPS O-antigen and showed that the O-antigen polysaccharide is an abundant extracellular carbohydrate of PA14. We present evidence that LPS-like material is found as a component of a biofilm matrix of P. aeruginosa.Peer reviewed: YesNRC publication: Ye

Decoding the Folding of Burkholderia glumae Lipase: Folding Intermediates En Route to Kinetic Stability

The lipase produced by Burkholderia glumae folds spontaneously into an inactive near-native state and requires a periplasmic chaperone to reach its final active and secretion-competent fold. The B. glumae lipase-specific foldase (Lif) is classified as a member of the steric-chaperone family of which the propeptides of α-lytic protease and subtilisin are the best known representatives. Steric chaperones play a key role in conferring kinetic stability to proteins. However, until present there was no solid experimental evidence that Lif-dependent lipases are kinetically trapped enzymes. By combining thermal denaturation studies with proteolytic resistance experiments and the description of distinct folding intermediates, we demonstrate that the native lipase has a kinetically stable conformation. We show that a newly discovered molten globule-like conformation has distinct properties that clearly differ from those of the near-native intermediate state. The folding fingerprint of Lif-dependent lipases is put in the context of the protease-prodomain system and the comparison reveals clear differences that render the lipase-Lif systems unique. Limited proteolysis unveils structural differences between the near-native intermediate and the native conformation and sets the stage to shed light onto the nature of the kinetic barrier

Genetic Analysis of Anti-Amoebae and Anti-Bacterial Activities of the Type VI Secretion System in Vibrio cholerae

A type VI secretion system (T6SS) was recently shown to be required for full virulence of Vibrio cholerae O37 serogroup strain V52. In this study, we systematically mutagenized each individual gene in T6SS locus and characterized their functions based on expression and secretion of the hemolysin co-regulated protein (Hcp), virulence towards amoebae of Dictyostelium discoideum and killing of Escherichia coli bacterial cells. We group the 17 proteins characterized in the T6SS locus into four categories: twelve (VipA, VipB, VCA0109–VCA0115, ClpV, VCA0119, and VasK) are essential for Hcp secretion and bacterial virulence, and thus likely function as structural components of the apparatus; two (VasH and VCA0122) are regulators that are required for T6SS gene expression and virulence; another two, VCA0121 and valine-glycine repeat protein G 3 (VgrG-3), are not essential for Hcp expression, secretion or bacterial virulence, and their functions are unknown; the last group is represented by VCA0118, which is not required for Hcp expression or secretion but still plays a role in both amoebae and bacterial killing and may therefore be an effector protein. We also showed that the clpV gene product is required for Dictyostelium virulence but is less important for killing E. coli. In addition, one vgrG gene (vgrG-2) outside of the T6SS gene cluster was required for bacterial killing but another (vgrG-1) was not. However, a bacterial killing defect was observed when vgrG-1 and vgrG-3 were both deleted. Several genes encoded in the same putative operon as vgrG-1 and vgrG-2 also contribute to virulence toward Dictyostelium but have a smaller effect on bacterial killing. Our results provide new insights into the functional requirements of V. cholerae's T6SS in the context of secretion as well as killing of bacterial and eukaryotic phagocytic cells

Geometagenomics illuminates the impact of agriculture on the distribution and prevalence of plant viruses at the ecosystem scale

Disease emergence events regularly result from human activities such as agriculture, which frequently brings large populations of genetically uniform hosts into contact with potential pathogens. Although viruses cause nearly 50% of emerging plant diseases, there is little systematic information about virus distribution across agro-ecological interfaces and large gaps in understanding of virus diversity in nature. Here we applied a novel landscape-scale geometagenomics approach to examine relationships between agricultural land use and distributions of plantassociated viruses in two Mediterranean-climate biodiversity hotspots (Western Cape region of South Africa and Rhône river delta region of France). In total, we analysed 1725 geo-referenced plant samples collected over two years from 4.5 × 4.5 km2 grids spanning farmlands and adjacent uncultivated vegetation. We found substantial virus prevalence (25.8–35.7%) in all ecosystems, but prevalence and identified family-level virus diversity were greatest in cultivated areas, with some virus families displaying strong agricultural associations. Our survey revealed 94 previously unknown virus species, primarily from uncultivated plants. This is the first effort to systematically evaluate plant-associated viromes across broad agro-ecological interfaces. Our findings indicate that agriculture substantially influences plant virus distributions and highlight the extent of current ignorance about the diversity and roles of viruses in nature