Lif, the lysostaphin immunity factor, complements FemB in staphylococcal peptidoglycan interpeptide bridge formation

The formation of the Staphylococcus aureus peptidoglycan pentaglycine interpeptide chain needs FemA and FemB for the incorporation of glycines Gly2-Gly3, and Gly4-Gly5, respectively. The lysostaphin immunity factor Lif was able to complement FemB, as could be shown by serine incorporation and by an increase in lysostaphin resistance in the wild-type as well as in a femB mutant. However, Lif could not substitute for FemA in femA or in femAB-null mutants. Methicillin resistance, which is dependent on functional FemA and FemB, was not complemented by Lif, suggesting that serine-substituted side chains are a lesser substrate for penicillin-binding protein PBP2′ in methicillin resistanc

X-ray bright active galactic nuclei in massive galaxy clusters III: New insights into the triggering mechanisms of cluster AGN

We present the results of a new analysis of the X-ray selected Active Galactic Nuclei (AGN) population in the vicinity of 135 of the most massive galaxy clusters in the redshift range of 0.2 < z < 0.9 observed with Chandra. With a sample of more than 11,000 X-ray point sources, we are able to measure, for the first time, evidence for evolution in the cluster AGN population beyond the expected evolution of field AGN. Our analysis shows that overall number density of cluster AGN scales with the cluster mass as $\sim M_{500}^{-1.2}$. There is no evidence for the overall number density of cluster member X-ray AGN depending on the cluster redshift in a manner different than field AGN, nor there is any evidence that the spatial distribution of cluster AGN (given in units of the cluster overdensity radius r_500) strongly depends on the cluster mass or redshift. The $M^{-1.2 \pm 0.7}$ scaling relation we measure is consistent with theoretical predictions of the galaxy merger rate in clusters, which is expected to scale with the cluster velocity dispersion, $\sigma$, as $\sim \sigma^{-3}$ or $\sim M^{-1}$. This consistency suggests that AGN in clusters may be predominantly triggered by galaxy mergers, a result that is further corroborated by visual inspection of Hubble images for 23 spectroscopically confirmed cluster member AGN in our sample. A merger-driven scenario for the triggering of X-ray AGN is not strongly favored by studies of field galaxies, however, suggesting that different mechanisms may be primarily responsible for the triggering of cluster and field X-ray AGN.Comment: 21 Pages, 8 figures, 5 tables. Submitted to MNRAS. Comments are welcome, and please request Steven Ehlert for higher resolution figure

Probing the extreme realm of AGN feedback in the massive galaxy cluster, RX J1532.9+3021

We present a detailed Chandra, XMM-Newton, VLA and HST analysis of one of the strongest cool core clusters known, RX J1532.9+3021 (z=0.3613). Using new, deep 90 ks Chandra observations, we confirm the presence of a western X-ray cavity or bubble, and report on a newly discovered eastern X-ray cavity. The total mechanical power associated with these AGN-driven outflows is (22+/-9)*10^44 erg/s, and is sufficient to offset the cooling, indicating that AGN feedback still provides a viable solution to the cooling flow problem even in the strongest cool core clusters. Based on the distribution of the optical filaments, as well as a jet-like structure seen in the 325 MHz VLA radio map, we suggest that the cluster harbours older outflows along the north to south direction. The jet of the central AGN is therefore either precessing or sloshing-induced motions have caused the outflows to change directions. There are also hints of an X-ray depression to the north aligned with the 325 MHz jet-like structure, which might represent the highest redshift ghost cavity discovered to date. We further find evidence of a cold front (r=65kpc) that coincides with the outermost edge of the western X-ray cavity and the edge of the radio mini-halo. The common location of the cold front with the edge of the radio mini-halo supports the idea that the latter originates from electrons being reaccelerated due to sloshing induced turbulence. Alternatively, its coexistence with the edge of the X-ray cavity may be due to cool gas being dragged out by the outburst. We confirm that the central AGN is highly sub-Eddington and conclude that a >10^10M_Sun or a rapidly spinning black hole is favoured to explain both the radiative-inefficiency of the AGN and the powerful X-ray cavities.Comment: Accepted for publication to ApJ (minor corrections), 16 pages, 16 figures, 5 tables. Full resolution at http://www.stanford.edu/~juliehl/M1532

X-ray Bright Active Galactic Nuclei in Massive Galaxy Clusters II: The Fraction of Galaxies Hosting Active Nuclei

We present a measurement of the fraction of cluster galaxies hosting X-ray bright Active Galactic Nuclei (AGN) as a function of clustercentric distance scaled in units of $r_{500}$. Our analysis employs high quality Chandra X-ray and Subaru optical imaging for 42 massive X-ray selected galaxy cluster fields spanning the redshift range of $0.2 < z < 0.7$. In total, our study involves 176 AGN with bright ($R <23$) optical counterparts above a $0.5-8.0$ keV flux limit of $10^{-14} \rm{erg} \ \rm{cm}^{-2} \ \rm{s}^{-1}$. When excluding central dominant galaxies from the calculation, we measure a cluster-galaxy AGN fraction in the central regions of the clusters that is $\sim 3$ times lower that the field value. This fraction increases with clustercentric distance before becoming consistent with the field at $\sim 2.5 r_{500}$. Our data exhibit similar radial trends to those observed for star formation and optically selected AGN in cluster member galaxies, both of which are also suppressed near cluster centers to a comparable extent. These results strongly support the idea that X-ray AGN activity and strong star formation are linked through their common dependence on available reservoirs of cold gas.Comment: 9 Pages, 4 Figures, accepted for publication in MNRAS, please contact Steven Ehlert ([email protected]) with any querie

Assessment of the molecular mechanisms of action of novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one allosteric modulators at the M1 muscarinic acetylcholine receptors

Positive allosteric modulators (PAMs) that target the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) are potential treatments for cognitive deficits in conditions such as Alzheimer's disease and schizophrenia. We recently reported novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one M1 mAChR PAMs with the potential to display different modes of positive allosteric modulation and/or agonism (Mistry et al., 2016), but their molecular mechanisms of action remain undetermined. The current study compared the pharmacology of three such novel PAMs with the prototypical first-generation PAM, BQCA, in a recombinant Chinese hamster ovary (CHO) cell line stably expressing the human M1 mAChR. Interactions between the orthosteric agonists and the novel PAMs or BQCA suggested their allosteric effects were solely governed by modulation of agonist affinity. The greatest degree of positive co-operativity was observed with higher efficacy agonists, whereas minimal potentiation was observed when the modulators were tested against the lower efficacy agonist, xanomeline. Each PAM was investigated for its effects on the endogenous agonist, ACh, on three different signalling pathways, (ERK1/2 phosphorylation, IP1 accumulation and β-arrestin-2 recruitment), revealing that the allosteric potentiation generally tracked with the efficiency of stimulus-response coupling and that there was little pathway bias in the allosteric effects. Thus, despite the identification of novel allosteric scaffolds targeting the M1 mAChR, the molecular mechanism of action of these compounds is largely consistent with a model of allostery previously described for BQCA, suggesting that this may be a more generalized mechanism for M1 mAChR PAM effects than previously appreciated

Molar and local effects of the fixed-ratio changeover requirement on choice, changeovers, and visits: A parametric examination of the fixed-ratio changeover requirement

The distribution of behavior by organisms in choice situations is of long-standing interest to psychologists. The generalized matching relation accurately predicts choice between concurrent variable-interval schedules of reinforcement. Researchers have assumed, on weak grounds, that the effect of the changeover requirement on sensitivity to reinforcement--the exponent in the generalized matching equation--was consistent. This experiment considered the effects of the changeover requirement by parametrically manipulating the fixed-ratio schedule required to switch alternatives. Pigeons pecked either of two side-response keys in a standard three-key operant chamber for food, delivered according to independent variable-interval schedules. No changeover delay was used, instead completion of five fixed-ratio schedules (FR 0, 2, 6, 12, or 20) on the center-response key alternated the active side key. Five reinforcer ratio (1:1, 1:2, 2:1, 1:4, and 4:1) were paired with most FR schedules. A matching relation analysis indicated that for two pigeons response-allocation sensitivity generally overmatched for all but the FR 0 condition, which undermatched. The other two pigeons\u27 sensitivity increased to overmatching when FR 12 was in force. Excepting FR 0 conditions, time-allocation sensitivity, on the other hand, decreased from extreme overmatching toward matching as the changeover requirement increased. Reliable changes in response rates to the two alternatives account for the results. A positive relation between the conditional probability of switching and run length is reported. That is, the greater the number of consecutive pecks to an alternative, the greater the likelihood of switching. This result suggests that behavior is controlled in part by local reinforcement contingencies. I speculate that factors that increase visit duration may increase local control of switching. The procedure encourages a foraging interpretation. The FR changeover requirement can be considered functionally equivalent to travel between patches. An analysis of visit measures supported earlier evidence that residence measures increase as travel between patches increases. These results together with the matching results suggest that behavior ecologists and operant psychologists are working on similar problems and the traditional tools of operant psychology can be used to simulate travel, an important component of foraging in the wild

X-ray Bright Active Galactic Nuclei in Massive Galaxy Clusters I: Number Counts and Spatial Distribution

We present an analysis of the X-ray bright point source population in 43 massive clusters of galaxies observed with the Chandra X-ray Observatory. We have constructed a catalog of 4210 rigorously selected X-ray point sources in these fields, which span a survey area of 4.2 square degrees. This catalog reveals a clear excess of sources when compared to deep blank-field surveys, which amounts to roughly 1 additional source per cluster, likely Active Galactic Nuclei (AGN) associated with the clusters. The excess sources are concentrated within the virial radii of the clusters, with the largest excess observed near the cluster centers. The average radial profile of the excess X-ray sources of the cluster are well described by a power law (N(r) ~ r^\beta) with an index of \beta ~ -0.5. An initial analysis using literature results on the mean profile of member galaxies in massive X-ray selected clusters indicates that the fraction of galaxies hosting X-ray AGN rises with increasing clustercentric radius, being approximately 5 to 10 times higher near the virial radius than in the central regions. This trend is qualitatively similar to that observed for star formation in cluster member galaxies.Comment: 18 Pages, 10 Figures, Submitted to MNRAS. Please contact Steven Ehlert ([email protected]) for higher resolution figures. Updated to reflect small changes requested by referee. This version has been accepted into MNRA

Extreme AGN Feedback and Cool Core Destruction in the X-ray Luminous Galaxy Cluster MACS J1931.8-2634

We report on a deep, multiwavelength study of the galaxy cluster MACS J1931.8-2634 using Chandra X-ray, Subaru optical, and VLA 1.4 GHz radio data. This cluster (z=0.352) harbors one of the most X-ray luminous cool cores yet discovered, with an equivalent mass cooling rate within the central 50 kpc is approximately 700 solar masses/yr. Unique features observed in the central core of MACSJ1931.8-2634 hint to a wealth of past activity that has greatly disrupted the original cool core. We observe a spiral of relatively cool, dense, X-ray emitting gas connected to the cool core, as well as highly elongated intracluster light (ICL) surrounding the cD galaxy. Extended radio emission is observed surrounding the central AGN, elongated in the east-west direction, spatially coincident with X-ray cavities. The power input required to inflate these `bubbles' is estimated from both the X-ray and radio emission to reside between 4 and 14e45 erg/s, putting it among the most powerful jets ever observed. This combination of a powerful AGN outburst and bulk motion of the cool core have resulted in two X-ray bright ridges to form to the north and south of the central AGN at a distance of approximately 25 kpc. The northern ridge has spectral characteristics typical of cool cores and is consistent with being a remnant of the cool core after it was disrupted by the AGN and bulk motions. It is also the site of H-alpha filaments and young stars. The X-ray spectroscopic cooling rate associated with this ridge is approximately 165 solar masses/yr, which agrees with the estimate of the star formation rate from broad-band optical imaging (170 solar masses/yr). MACS J1931.8-2634 appears to harbor one of most profoundly disrupted low entropy cores observed in a cluster, and offers new insights into the survivability of cool cores in the context of hierarchical structure formation.Comment: 19 pages, 15 figures, 5 tables. Accepted by MNRAS for publication September 30 201